T-DM1 vs Paclitaxel/Trastuzumab for Breast (ATEMPT Trial)
Study Details
Study Description
Brief Summary
This research study is a Phase II clinical trial. Phase II clinical trials test the effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is still being studied and that research doctors are trying to find out more about it-such as the safest dose to use, the side effects it may cause, and if the drug is effective for treating different types of cancer. It also means that the FDA has not approved this drug for use patients undergoing adjuvant treatment for HER2+ breast cancer. Trastuzumab emtansine (T-DM1) is a drug that may stop cancer cells from growing. This drug has been used in other research studies and information from those other research studies suggests that this drug may help to prevent the recurrence of breast cancer in this research study.
The use of T-DM1 in this research study is experimental, which means it is not approved by any regulatory authority for the adjuvant treatment of HER2-positive breast cancer. However, it FDA-approved for metastatic HER2-positive breast cancer. T-DM1 has caused cancer cells to die in laboratory studies. In preclinical studies, this drug has prevented or slowed the growth of breast cancer. The breast cancer treatments (paclitaxel and Trastuzumab) used in this study are considered part of standard-of-care regimens in early breast cancer. A standard treatment means that this is a treatment that would be accepted by the majority of the medical community as a suitable treatment for your type of breast cancer.
In this research study, the investigators are looking to see if the study drug T-DM1 will have less side effects than traditional HER2-positive breast cancer treatment of trastuzumab and paclitaxel. The investigators are also hoping to learn about the long term benefits and disease-free survival of participants who take the study drug T-DM1 in comparison to those participants to take the combination of trastuzumab and paclitaxel.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
If a participant agrees to participate in this study she will be asked to undergo some screening tests or procedures to confirm that she is eligible. Many of these tests and procedures are likely to be part of regular cancer care and may be done even if turns out that she does not take part in this research study. If she has had some of these tests or procedures recently, they may or may not have to be repeated. These tests and procedures will include: a medical history, performance status, assessment of your tumor, blood tests, cardiac tests, pregnancy test and a collection of tumor tissue. If these tests show that she is eligible to participate in the research study, she will begin the study treatment. If she does not meet the eligibility criteria, she will not be able to participate in this research study.
Because no one knows which of the study options is best, the participant will be "randomized" into one of the study groups after she has had her breast surgery: Group 1 or Group 2. Randomization means that she is put into a group by chance. Neither the participant nor the research doctor will choose what group she will be in. The participant will have a one in three chance of being placed in any group. Approximately 375 study participants will receive the study drug, while 125 study participants will receive the standard therapy of trastuzumab and paclitaxel.
Group 1 participants will receive the study drug T-DM1 every three weeks by IV (intravenous injection) for 17 treatments (total of 51 weeks).
Group 2 participants will receive the FDA-approved drugs Paclitaxel and Trastuzumab once per week by IV for 12 weeks. Then beginning week 13, participants will receive Trastuzumab only by IV injection every three weeks for the next 13 treatments.
During all cycles the participant will have a physical exam and tumor assessment.
The investigators would like to keep track of the participant's medical condition for the next five years after the final dose of study drug. The investigators would like to do this by regular visits every 6 months for 3 years after completion of study treatment, and then once a year for the next two years. The investigators may ask for additional follow-up by phone after completion of these visits.
Participants who undergo lumpectomy (breast conserving surgery) need to receive breast radiation therapy to participate in this study. Participants who have undergone a mastectomy may receive chest wall and lymph node radiation (as determined by discussion with their physician). Radiation Therapy will begin after the conclusion of all study paclitaxel doses, and after 12 weeks fo the study drug T-DM1.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Trastuzumab emtansine (T-DM1) T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks |
Drug: Trastuzumab emtansine
Other Names:
|
| Active Comparator: Paclitaxel + Trastuzumab paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
Drug: Trastuzumab
Drug: Paclitaxel
|
Outcome Measures
Primary Outcome Measures
- Number of Participants of Clinically Relevant Toxicities (CRT) [5 years after completion of study treatment or until death, whichever occurs first.]
Clinically relevant toxicities will include the composite incidence of grade 3 or higher non-hematologic toxicity, grade 2 or higher neurotoxicity, and grade 4 or higher hematologic toxicity. These toxicities will only be assessed at the pre-specified toxicity-assessment visits. In addition, the following events, regardless of timing of their occurrence, will also count towards the composite endpoint: febrile neutropenia, any toxicity requiring dose-delay, discontinuation of any study treatment (Paclitaxel, Trastuzumab, or T-DM1) for toxicity, and any serious adverse event (SAE).
- 3-year Disease Free Survival (DFS) Rate of Trastuzumab Emtansine (TDM-1) [3 years]
Disease-free survival (DFS) is evaluated and defined per protocol: from the time of randomization until the to the occurrence of the first of the following events: Local/regional recurrence: a recurrent or new invasive ipsilateral breast cancer, invasive breast cancer in the axilla, regional lymph nodes, chest wall, or skin of the ipsilateral breast. Contralateral invasive breast cancer, Distant recurrence: metastatic disease that has either been biopsy confirmed or clinically diagnosed as recurrent invasive breast cancer. A single new lesion on a bone scan without evidence of lytic disease on x-ray and without symptoms does not in and of itself constitute distant recurrence, but multiple new bone lesions, or increased isotope uptake associated with new bone symptoms are more likely due to metastases. Bone metastases must be documented with x-rays and clinical description. Death from any cause
Secondary Outcome Measures
- Incidence Rate of Grade 3-4 Treatment-Related Toxicity [AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years.]
All grade 3 - 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade >=3 AE of any type during the time of observation.
- Quality of Life (QOL) FACT B Total Score at Baseline [at baseline]
The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below: Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well).
- Quality of Life (QOL) FACT B Total Score at Week 3 [at week 3]
The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below: Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well).
- Quality of Life (QOL) FACT B Total Score at Week 12 [at week 12]
The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below: Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well).
- Quality of Life (QOL) FACT B Total Score at 6 Months [at 6 months]
The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below: Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well).
- Quality of Life (QOL) FACT B Total Score at 1 Year [at 1 year]
The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below: Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well).
- Quality of Life (QOL) FACT B Total Score at 18 Months [at 18 months]
The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below: Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well).
- Quality of Life (QOL) FACT B Total Score at 24 Months [at 24 months]
The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below: Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well).
- Number of Patients Has Neuropathy [Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18. The data cutoff date is 18 month.]
Neuropathy evaluated by Patient Neurotoxicity Questionnaire (PNQ) defined per protocol.
- Percentage of Work Time Missed Because of Health [Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up.]
Effects of therapy on work productivity and activity - work time missed because of health, evaluated using the Work Productivity and Activity Impairment Questionnaire (WPAI-SHP), which defined per protocol.
- Percentage of Impairment While Working Because of Health (Mean, SD) [Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up.]
Effects of therapy on work productivity and activity - Impairment While Working because of health, evaluated using the Work Productivity and Activity Impairment Questionnaire (WPAI-SHP), which defined per protocol.
- Percentage of Overall Work Impairment Because of Health [Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up.]
Effects of therapy on work productivity and activity - Work Impairment because of health, evaluated using the Work Productivity and Activity Impairment Questionnaire (WPAI-SHP), which defined per protocol.
- Percentage of Activity Impairment Because of Health [Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up.]
Effects of therapy on work productivity and activity - Activity Impairment because of health, evaluated using the Work Productivity and Activity Impairment Questionnaire (WPAI-SHP), which defined per protocol.
- Number of Patients Have Alopecia [Median follow-up was 3.9 years. The AE data cutoff date is 21 April 2020.]
alopecia assessment is a 5-item questionnaire that will assess the impact alopecia has had on these patients and will be conducted electronically at pre-specified study visits. If electronic evaluation is not possible, paper evaluation will be conducted.
- 3-year T-DM1 iDFS Percentage by Tumor Size and Hormone Receptor (HR) Status [3 years]
Disease-free survival (DFS) is evaluated in patients treated with trastuzumab emtansine, which is defined per protocol: from the time of randomization until the to the occurrence of the first of the following events: Local/regional recurrence: a recurrent or new invasive ipsilateral breast cancer, invasive breast cancer in the axilla, regional lymph nodes, chest wall, or skin of the ipsilateral breast. Contralateral invasive breast cancer, Distant recurrence: metastatic disease that has either been biopsy confirmed or clinically diagnosed as recurrent invasive breast cancer. A single new lesion on a bone scan without evidence of lytic disease on x-ray and without symptoms does not in and of itself constitute distant recurrence, but multiple new bone lesions, or increased isotope uptake associated with new bone symptoms are more likely due to metastases. Bone metastases must be documented with x-rays and clinical description. Death from any cause
- Number of Incidence of Grade 3-4 Cardiac Left Ventricular Dysfunction [AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years.]
All grade 3 - 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade >=3 AE of any type during the time of observation
- Number of Incidence of T-DM1 Induced Grade 2-3 Thrombocytopenia [AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years.]
Reversible Grade 1-4 thrombocytopenia has been observed in ongoing studies with trastuzumab emtansine.
- Gene Biomarkers Predictive of Trastuzumab Emtansine-induced Grade 2-4 Thrombocytopenia [May 17, 2013, and December 13, 2016]
- Percentage of Patients With Amenorrhea [Surveys are took at month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up.]
All grade 3 - 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade >=3 AE of any type during the time of observation. For those who were premenopausal pre-chemotherapy, at each follow-up visit (every six months) in order to assess for duration of amenorrhea and also premature ovarian failure.
- Gene Mutation Assessed Using High-throughput Mutation Profiling System (Oncomap) [After treatment]
Archival tumor tissue from all patients will be assessed using a high-throughput mutation profiling system (Oncomap) to query a large panel of cancer gene mutations.
- Median Overall Survival (OS) [Reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first.]
OS is evaluated in patients with Stage I HER2-positive breast cancer treated with trastuzumab emtansine
Eligibility Criteria
Criteria
Inclusion Criteria:
-
HER2-positive Stage I histologically confirmed invasive carcinoma of the breast
-
ER/PR determination is required
-
HER2 positive, confirmed by central testing: IHC 3+, FISH HER2/CEP17 <2.0 with an average HER2 copy number >/=6.0, or FISH HER2/CEP17 >/= 2.0
-
Bilateral breast cancers that individually meet eligibility criteria are allowed
-
Subjects with multifocal or multicentric disease are eligible as long as each tumor individually meets eligibility criteria
-
Subjects with a history of ipsilateral DCIS are eligible if they were treated with wide-excision alone, without radiation therapy; Patients with a history of contralateral DCIS are not eligible.
-
Should have tumor tissue available and a tissue block of sufficient size to make 15 slides, which must be sent to a DFCI site for testing
-
Less than or equal to 90 days since most recent breast surgery for this breast cancer
-
All tumor should be removed by either a modified radical mastectomy or a segmental mastectomy (lumpectomy) with either a sentinel node biopsy or axillary dissection
-
All margins should be clear of invasive cancer or DCIS
-
May have received up to 4 weeks of tamoxifen therapy or other hormonal therapy, for adjuvant therapy for this cancer
-
Prior oophorectomy for cancer prevention is allowed
-
Subjects who have undergone partial breast radiation (duration </= 7 days) prior to registration are eligible. Partial breast radiation must be completed prior to 2 weeks before starting protocol therapy.
-
Must have discontinued any investigational drug at least 2 weeks prior to participation
-
Willing to use one highly effective from of nonhormonal contraception or two effective forms of nonhormonal contraception while on study and for 7 months after end of study treatment
-
Subjects undergoing lumpectomy must have no contraindications to radiation therapy
Exclusion Criteria:
-
Pregnant or breastfeeding
-
Use of potent CYP3A4 inhibitors during the study treatment period
-
Excessive alcohol intake (more than 3 alcoholic beverages per day)
-
Locally advanced tumors at diagnosis
-
History of previous invasive breast cancer
-
History of prior chemotherapy in the past 5 years
-
History of prior trastuzumab or prior paclitaxel therapy
-
Active, unresolved infection
-
Active liver disease
-
History of a different malignancy except for the following: disease free for at least 5 years and at low risk for recurrence; cervical cancer in situ, basal or squamous cell carcinoma of the skin
-
Active cardiac disease
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama Birmingham | Birmingham | Alabama | United States | 35249 |
| 2 | University of California San Francisco | San Francisco | California | United States | 94115 |
| 3 | Hartford Hospital | Hartford | Connecticut | United States | 06102 |
| 4 | Midstate Medical Center | Meriden | Connecticut | United States | 06451 |
| 5 | Hartford Healthcare Cancer Institute at The Hospital of Central Connecticut | New Britain | Connecticut | United States | 06050 |
| 6 | William W Backus Hospital | Norwich | Connecticut | United States | 06360 |
| 7 | Georgetown Hospital | Washington | District of Columbia | United States | 20007 |
| 8 | Washington Cancer Institute at Medstar Washington Hospital Center | Washington | District of Columbia | United States | 20010 |
| 9 | Sibley Memorial Hospital | Washington | District of Columbia | United States | 20016 |
| 10 | Florida Cancer Specialists | Fort Myers | Florida | United States | 33916 |
| 11 | Florida Cancer Specialists | Saint Petersburg | Florida | United States | 337054 |
| 12 | Mountain States Tumor Institute | Boise | Idaho | United States | 83712 |
| 13 | Mountain States Tumor Institute | Fruitland | Idaho | United States | 83619 |
| 14 | Mountain States Tumor Institute | Meridian | Idaho | United States | 83642 |
| 15 | Mountain States Tumor Institute | Nampa | Idaho | United States | 83686 |
| 16 | Mountain States Tumor Institute | Twin Falls | Idaho | United States | 83301 |
| 17 | Loyola University Medical Center | Maywood | Illinois | United States | 60153 |
| 18 | University of Chicago Comprehensive Cancer Center at Silver Cross Hospital | New Lenox | Illinois | United States | 60451 |
| 19 | University of Chicago Medical Center for Advanced Care Orland Park | Orland Park | Illinois | United States | 60462 |
| 20 | Indiana University - Wishard Hospital | Indianapolis | Indiana | United States | 46202 |
| 21 | Indiana University Health - Melvin and Bren Simon Cancer Center | Indianapolis | Indiana | United States | 46202 |
| 22 | Indiana University Health - University Hospital | Indianapolis | Indiana | United States | 46202 |
| 23 | Indiana University - Springmill Medical Clinic | Indianapolis | Indiana | United States | 46290 |
| 24 | Eastern Maine Medical Center's Cancer Care | Brewer | Maine | United States | 04412 |
| 25 | Johns Hopkins - Sidney Kimmel Comprehensive Cancer Center | Baltimore | Maryland | United States | 21287 |
| 26 | Suburban Hospital Cancer Program | Bethesda | Maryland | United States | 20817 |
| 27 | Johns Hopkins - Green Spring Station | Lutherville | Maryland | United States | 21093 |
| 28 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 29 | Dana Farber Cancer Institute at Faulkner Hospital | Boston | Massachusetts | United States | 02130 |
| 30 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
| 31 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 32 | Mass General North Shore Cancer Center | Danvers | Massachusetts | United States | 01923 |
| 33 | Lowell General Hospital | Lowell | Massachusetts | United States | 01854 |
| 34 | Dana-Farber Cancer Institute at Milford Hospital | Milford | Massachusetts | United States | 01757 |
| 35 | Univeristy of Michigan Health System | Ann Arbor | Michigan | United States | 48109 |
| 36 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 37 | Barnes-Jewish Hospital | Saint Louis | Missouri | United States | 63110 |
| 38 | Washington University, School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 39 | Siteman Cancer Center - South County | Saint Louis | Missouri | United States | 63129 |
| 40 | Siteman Cancer Center - West County | Saint Louis | Missouri | United States | 63141 |
| 41 | Siteman Cancer Center - St. Peters | Saint Peters | Missouri | United States | 63376 |
| 42 | New Hampshire Oncology-Hematology, PA | Concord | New Hampshire | United States | 03301 |
| 43 | New Hampshire Oncology-Hematology, PA | Hooksett | New Hampshire | United States | 03106 |
| 44 | New Hampshire Oncology-Hematology, PA | Laconia | New Hampshire | United States | 03246 |
| 45 | Dana-Farber Cancer Insitute at Londonderry Hospital | Londonderry | New Hampshire | United States | 03053 |
| 46 | Memorial Sloan Kettering Cancer Center-Basking Ridge | Basking Ridge | New Jersey | United States | 07920 |
| 47 | Memorial Sloan Kettering Cancer Center-Suffolk | Commack | New York | United States | 11725 |
| 48 | Memorial Sloan Kettering Cancer Center Westchester | Harrison | New York | United States | 10604 |
| 49 | Queens Hospital Center, Comprehensive Cancer Center | Jamaica | New York | United States | 11432 |
| 50 | Northwell Health/Monter Cancer Center | Lake Success | New York | United States | 11042 |
| 51 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 52 | Memorial Sloan Kettering Cancer Center-Mercy | Rockville Centre | New York | United States | 11570 |
| 53 | Memorial Sloan Kettering Cancer Center-Sleepy Hollow | Sleepy Hollow | New York | United States | 10591 |
| 54 | University of North Carolina | Chapel Hill | North Carolina | United States | 27599 |
| 55 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 56 | Rex Cancer Center | Raleigh | North Carolina | United States | 27607 |
| 57 | The Ohio State University | Columbus | Ohio | United States | 43212 |
| 58 | Lehigh Valley Hospital/Lehigh Valley Health Network | Allentown | Pennsylvania | United States | 18103 |
| 59 | UPMC/HVHS Cancer Center, UPMC Beaver | Beaver | Pennsylvania | United States | 15143 |
| 60 | UPMC CancerCenters Butler | Butler | Pennsylvania | United States | 16001 |
| 61 | UPMC Horizon (Shenango) | Farrell | Pennsylvania | United States | 16121 |
| 62 | Arnold Palmer Cancer Center-Greensburg | Greensburg | Pennsylvania | United States | 15601 |
| 63 | Arnold Palmer Medical Oncology Oakbrook | Greensburg | Pennsylvania | United States | 15642 |
| 64 | UPMC Horizon (Greenville) | Greenville | Pennsylvania | United States | 16125 |
| 65 | UPMC Pinnacle Harrisburg | Harrisburg | Pennsylvania | United States | 17101 |
| 66 | UPMC Cancer Center Jefferson Regional Med Ctr | Jefferson Hills | Pennsylvania | United States | 15025 |
| 67 | UPMC Conemaugh Cancer Center | Johnstown | Pennsylvania | United States | 15905 |
| 68 | UPMC McKeesport | McKeesport | Pennsylvania | United States | 15132 |
| 69 | UPMC East | Monroeville | Pennsylvania | United States | 15146 |
| 70 | Arnold Palmer Medical Oncology-Mt Pleasant | Mount Pleasant | Pennsylvania | United States | 15666 |
| 71 | UPMC Jameson Cancer Center | New Castle | Pennsylvania | United States | 16105 |
| 72 | UPMC St. Margaret | Pittsburgh | Pennsylvania | United States | 15215 |
| 73 | UPMC Cancer Center St. Clair Hospital | Pittsburgh | Pennsylvania | United States | 15232 |
| 74 | UPMC Presbyterian Shadyside | Pittsburgh | Pennsylvania | United States | 15232 |
| 75 | UPMC Passavant | Pittsburgh | Pennsylvania | United States | 15237 |
| 76 | UPMC Northwest (Franklin) | Seneca | Pennsylvania | United States | 16346 |
| 77 | UPMC Northwest (Oil City) | Seneca | Pennsylvania | United States | 16346 |
| 78 | UPMC and the Washington Hospital Center | Washington | Pennsylvania | United States | 15301 |
| 79 | Tennessee Oncology/Sarah Cannon Research Institute | Nashville | Tennessee | United States | 37203 |
| 80 | Vanderbilt-Ingram Cancer Center | Nashville | Tennessee | United States | 37232 |
| 81 | Baylor College of Medicine-Baylor Clinic | Houston | Texas | United States | 77030 |
| 82 | Harris County Hospital District-Ben Taub General Hospital | Houston | Texas | United States | 77030 |
| 83 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 84 | Harris County Hospital District-Smith Clinic | Houston | Texas | United States | 77054 |
| 85 | University of Washington Seattle Cancer Care Alliance | Seattle | Washington | United States | 98109 |
Sponsors and Collaborators
- Dana-Farber Cancer Institute
Investigators
- Principal Investigator: Sara Tolaney, MD, MPH, Dana-Farber Cancer Institute
Study Documents (Full-Text)
More Information
Publications
None provided.- 13-048
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab (TH) |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Period Title: Allocation | ||
| STARTED | 384 | 128 |
| COMPLETED | 383 | 114 |
| NOT COMPLETED | 1 | 14 |
| Period Title: Allocation | ||
| STARTED | 383 | 114 |
| COMPLETED | 293 | 97 |
| NOT COMPLETED | 90 | 17 |
Baseline Characteristics
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab (TH) | Total |
|---|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments | Total of all reporting groups |
| Overall Participants | 383 | 114 | 497 |
| Age (Years) [Median (Full Range) ] | |||
| Median (Full Range) [Years] |
56
|
55
|
56
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
383
100%
|
114
100%
|
497
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| White |
327
85.4%
|
93
81.6%
|
420
84.5%
|
| Black or African American |
21
5.5%
|
7
6.1%
|
28
5.6%
|
| Asian |
22
5.7%
|
4
3.5%
|
26
5.2%
|
| More than one race |
2
0.5%
|
1
0.9%
|
3
0.6%
|
| Other |
11
2.9%
|
9
7.9%
|
20
4%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
383
100%
|
114
100%
|
497
100%
|
Outcome Measures
| Title | Number of Participants of Clinically Relevant Toxicities (CRT) |
|---|---|
| Description | Clinically relevant toxicities will include the composite incidence of grade 3 or higher non-hematologic toxicity, grade 2 or higher neurotoxicity, and grade 4 or higher hematologic toxicity. These toxicities will only be assessed at the pre-specified toxicity-assessment visits. In addition, the following events, regardless of timing of their occurrence, will also count towards the composite endpoint: febrile neutropenia, any toxicity requiring dose-delay, discontinuation of any study treatment (Paclitaxel, Trastuzumab, or T-DM1) for toxicity, and any serious adverse event (SAE). |
| Time Frame | 5 years after completion of study treatment or until death, whichever occurs first. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 383 | 114 |
| Grade 3 or higher non-hematologic toxicity |
36
9.4%
|
13
11.4%
|
| Grade 2 or higher neurotoxicity |
42
11%
|
26
22.8%
|
| Grade 4 or higher hematologic toxicity |
4
1%
|
0
0%
|
| Febrile neutropenia |
0
0%
|
2
1.8%
|
| Any toxicity requiring dose delay |
106
27.7%
|
30
26.3%
|
| Any toxicity requiring early discontinuation of protocol therapy |
67
17.5%
|
7
6.1%
|
| Serious adverse event |
11
2.9%
|
6
5.3%
|
| Title | 3-year Disease Free Survival (DFS) Rate of Trastuzumab Emtansine (TDM-1) |
|---|---|
| Description | Disease-free survival (DFS) is evaluated and defined per protocol: from the time of randomization until the to the occurrence of the first of the following events: Local/regional recurrence: a recurrent or new invasive ipsilateral breast cancer, invasive breast cancer in the axilla, regional lymph nodes, chest wall, or skin of the ipsilateral breast. Contralateral invasive breast cancer, Distant recurrence: metastatic disease that has either been biopsy confirmed or clinically diagnosed as recurrent invasive breast cancer. A single new lesion on a bone scan without evidence of lytic disease on x-ray and without symptoms does not in and of itself constitute distant recurrence, but multiple new bone lesions, or increased isotope uptake associated with new bone symptoms are more likely due to metastases. Bone metastases must be documented with x-rays and clinical description. Death from any cause |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 383 | 114 |
| Number (95% Confidence Interval) [proportion of participants] |
0.978
0.3%
|
0.934
0.8%
|
| Title | Incidence Rate of Grade 3-4 Treatment-Related Toxicity |
|---|---|
| Description | All grade 3 - 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade >=3 AE of any type during the time of observation. |
| Time Frame | AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 383 | 114 |
| Number (95% Confidence Interval) [proportion of participants] |
0.16
0%
|
0.23
0.2%
|
| Title | Quality of Life (QOL) FACT B Total Score at Baseline |
|---|---|
| Description | The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below: Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well). |
| Time Frame | at baseline |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab (TH) |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 351 | 103 |
| Mean (Standard Deviation) [score on a scale] |
126.25
(14.29)
|
116.69
(19.03)
|
| Title | Quality of Life (QOL) FACT B Total Score at Week 3 |
|---|---|
| Description | The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below: Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well). |
| Time Frame | at week 3 |
Outcome Measure Data
| Analysis Population Description |
|---|
| not all patients required to complete the QOL |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 326 | 89 |
| Mean (Standard Deviation) [score on a scale] |
127.07
(14.52)
|
116.6
(18.9)
|
| Title | Quality of Life (QOL) FACT B Total Score at Week 12 |
|---|---|
| Description | The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below: Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well). |
| Time Frame | at week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| not all patients required to complete the QOL |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 302 | 83 |
| Mean (Standard Deviation) [score on a scale] |
124.36
(16.3)
|
108.25
(23.33)
|
| Title | Quality of Life (QOL) FACT B Total Score at 6 Months |
|---|---|
| Description | The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below: Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well). |
| Time Frame | at 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| not all patients required to complete the QOL |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 299 | 83 |
| Mean (Standard Deviation) [score on a scale] |
123
(16.71)
|
118.16
(21.73)
|
| Title | Quality of Life (QOL) FACT B Total Score at 1 Year |
|---|---|
| Description | The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below: Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well). |
| Time Frame | at 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| not all patients required to complete the QOL |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 276 | 87 |
| Mean (Standard Deviation) [score on a scale] |
123.29
(16.44)
|
120.3
(20.88)
|
| Title | Quality of Life (QOL) FACT B Total Score at 18 Months |
|---|---|
| Description | The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below: Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well). |
| Time Frame | at 18 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| not all patients required to complete the QOL |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 279 | 77 |
| Mean (Standard Deviation) [score on a scale] |
126.42
(15.67)
|
117.93
(23.55)
|
| Title | Quality of Life (QOL) FACT B Total Score at 24 Months |
|---|---|
| Description | The QOL assessments questionnaire should be completed via the tablet provided by the study or on any available computer with an internet connection. The FACT-B questionnaire consists of five subscale, listed below: Physical well being(PWB): range 0-28 Social/Family well being(SWB): range 0-28 Emotional well being(EWB): range 0-24 Functional well being(FWB): range 0-28 Breast cancer subscale(BCS): range 0-40 The total score (FACTB) is calculated by summarizing all the subscales listed above, therefore it ranges from 0 to 148. The higher the score the better the outcome (applies to all sub-scales as well). |
| Time Frame | at 24 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| not all patients required to complete the QOL |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 260 | 71 |
| Mean (Standard Deviation) [score on a scale] |
127.19
(16.16)
|
121.73
(22.00)
|
| Title | Number of Patients Has Neuropathy |
|---|---|
| Description | Neuropathy evaluated by Patient Neurotoxicity Questionnaire (PNQ) defined per protocol. |
| Time Frame | Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18. The data cutoff date is 18 month. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PNQ analysis was done on patients that completed at least baseline questionnaires and at least one follow-up questionnaire. Some patients did not complete this questionnaire at either baseline or follow-up. This is the reason for the reduced number of patients when reporting PNQ results. |
| Arm/Group Title | T-DM1 With no Baseline Neuropathy | TH With no Baseline Neuropathy | T-DM1 With Any Baseline Neuropathy | TH With Any Baseline Neuropathy |
|---|---|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. No neuropathy at baseline | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. No neuropathy at baseline | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks. Neuropathy at baseline | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments. Neuropathy at baseline |
| Measure Participants | 291 | 81 | 58 | 23 |
| No, mild, or moderate neuropathy |
267
69.7%
|
64
56.1%
|
36
7.2%
|
11
NaN
|
| Moderate to severe and severe neuropathy |
24
6.3%
|
17
14.9%
|
22
4.4%
|
12
NaN
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Trastuzumab Emtansine (T-DM1), Paclitaxel + Trastuzumab, T-DM1 With Any Baseline Neuropathy, TH With Any Baseline Neuropathy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0012 |
| Comments | ||
| Method | Mantel Haenszel | |
| Comments | ||
| Title | Percentage of Work Time Missed Because of Health |
|---|---|
| Description | Effects of therapy on work productivity and activity - work time missed because of health, evaluated using the Work Productivity and Activity Impairment Questionnaire (WPAI-SHP), which defined per protocol. |
| Time Frame | Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 383 | 114 |
| Baseline |
22
(35)
|
25
(34)
|
| 3 weeks |
13
(28)
|
27
(36)
|
| 12 weeks |
9
(21)
|
22
(33)
|
| 6 months |
8
(21)
|
7
(18)
|
| 12 months |
8
(21)
|
8
(20)
|
| 18 months |
3
(13)
|
4
(16)
|
| Title | Percentage of Impairment While Working Because of Health (Mean, SD) |
|---|---|
| Description | Effects of therapy on work productivity and activity - Impairment While Working because of health, evaluated using the Work Productivity and Activity Impairment Questionnaire (WPAI-SHP), which defined per protocol. |
| Time Frame | Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks Trastuzumab emtansine | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments Trastuzumab Paclitaxel |
| Measure Participants | 383 | 114 |
| Baseline |
10
(18)
|
20
(26)
|
| 3 weeks |
9
(16)
|
21
(25)
|
| 12 weeks |
11
(18)
|
21
(26)
|
| 6 months |
9
(14)
|
11
(19)
|
| 12 months |
12
(20)
|
9
(18)
|
| 18 months |
3
(8)
|
8
(17)
|
| Title | Percentage of Overall Work Impairment Because of Health |
|---|---|
| Description | Effects of therapy on work productivity and activity - Work Impairment because of health, evaluated using the Work Productivity and Activity Impairment Questionnaire (WPAI-SHP), which defined per protocol. |
| Time Frame | Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab (TH) |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 383 | 114 |
| Baseline |
19
(26)
|
31
(31)
|
| 3 weeks |
14
(23)
|
30
(29)
|
| 12 weeks |
16
(22)
|
29
(29)
|
| 6 months |
13
(18)
|
14
(22)
|
| 12 months |
16
(24)
|
13
(22)
|
| 18 months |
4
(12)
|
9
(18)
|
| Title | Percentage of Activity Impairment Because of Health |
|---|---|
| Description | Effects of therapy on work productivity and activity - Activity Impairment because of health, evaluated using the Work Productivity and Activity Impairment Questionnaire (WPAI-SHP), which defined per protocol. |
| Time Frame | Surveys are took at week 3, 12 and month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab (TH) |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 383 | 114 |
| Baseline |
14
(22)
|
22
(26)
|
| 3 weeks |
12
(19)
|
22
(27)
|
| 12 weeks |
13
(19)
|
33
(31)
|
| 6 months |
15
(21)
|
17
(22)
|
| 12 months |
15
(21)
|
14
(23)
|
| 18 months |
7
(17)
|
15
(27)
|
| Title | Number of Patients Have Alopecia |
|---|---|
| Description | alopecia assessment is a 5-item questionnaire that will assess the impact alopecia has had on these patients and will be conducted electronically at pre-specified study visits. If electronic evaluation is not possible, paper evaluation will be conducted. |
| Time Frame | Median follow-up was 3.9 years. The AE data cutoff date is 21 April 2020. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 383 | 114 |
| Count of Participants [Participants] |
157
41%
|
0
0%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Trastuzumab Emtansine (T-DM1), Paclitaxel + Trastuzumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | ||
| Method | Regression, Linear | |
| Comments | ||
| Title | 3-year T-DM1 iDFS Percentage by Tumor Size and Hormone Receptor (HR) Status |
|---|---|
| Description | Disease-free survival (DFS) is evaluated in patients treated with trastuzumab emtansine, which is defined per protocol: from the time of randomization until the to the occurrence of the first of the following events: Local/regional recurrence: a recurrent or new invasive ipsilateral breast cancer, invasive breast cancer in the axilla, regional lymph nodes, chest wall, or skin of the ipsilateral breast. Contralateral invasive breast cancer, Distant recurrence: metastatic disease that has either been biopsy confirmed or clinically diagnosed as recurrent invasive breast cancer. A single new lesion on a bone scan without evidence of lytic disease on x-ray and without symptoms does not in and of itself constitute distant recurrence, but multiple new bone lesions, or increased isotope uptake associated with new bone symptoms are more likely due to metastases. Bone metastases must be documented with x-rays and clinical description. Death from any cause |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) With Tumor Size < 1 cm | Trastuzumab Emtansine (T-DM1) With Tumor Size >= 1 cm |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks |
| Measure Participants | 163 | 220 |
| Number (95% Confidence Interval) [percentage of participants] |
98.7
25.8%
|
97.2
85.3%
|
| Title | Number of Incidence of Grade 3-4 Cardiac Left Ventricular Dysfunction |
|---|---|
| Description | All grade 3 - 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade >=3 AE of any type during the time of observation |
| Time Frame | AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab (TH) |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 383 | 114 |
| Count of Participants [Participants] |
3
0.8%
|
2
1.8%
|
| Title | Number of Incidence of T-DM1 Induced Grade 2-3 Thrombocytopenia |
|---|---|
| Description | Reversible Grade 1-4 thrombocytopenia has been observed in ongoing studies with trastuzumab emtansine. |
| Time Frame | AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 383 | 114 |
| Count of Participants [Participants] |
42
11%
|
1
0.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Trastuzumab Emtansine (T-DM1), Paclitaxel + Trastuzumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0001 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Gene Biomarkers Predictive of Trastuzumab Emtansine-induced Grade 2-4 Thrombocytopenia |
|---|---|
| Description | |
| Time Frame | May 17, 2013, and December 13, 2016 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Percentage of Patients With Amenorrhea |
|---|---|
| Description | All grade 3 - 4 adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv4 as reported on case report forms were counted. Incidence is the number of patients experiencing at least one treatment-related grade >=3 AE of any type during the time of observation. For those who were premenopausal pre-chemotherapy, at each follow-up visit (every six months) in order to assess for duration of amenorrhea and also premature ovarian failure. |
| Time Frame | Surveys are took at month 6 and 12 during treatment, and month 18, 24, 30 and 36 during follow up. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab (TH) |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 383 | 114 |
| 6 months |
80
20.9%
|
21
18.4%
|
| 1 year |
71
18.5%
|
22
19.3%
|
| 18 months |
64
16.7%
|
20
17.5%
|
| 24 months |
74
19.3%
|
15
13.2%
|
| 30 months |
60
15.7%
|
11
9.6%
|
| 36 months |
45
11.7%
|
9
7.9%
|
| Title | Gene Mutation Assessed Using High-throughput Mutation Profiling System (Oncomap) |
|---|---|
| Description | Archival tumor tissue from all patients will be assessed using a high-throughput mutation profiling system (Oncomap) to query a large panel of cancer gene mutations. |
| Time Frame | After treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| no genomic data were collected using the Oncomap system |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab (TH) |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 0 | 0 |
| Title | Median Overall Survival (OS) |
|---|---|
| Description | OS is evaluated in patients with Stage I HER2-positive breast cancer treated with trastuzumab emtansine |
| Time Frame | Reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab (TH) |
|---|---|---|
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments |
| Measure Participants | 383 | 114 |
| Number (95% Confidence Interval) [months] |
NA
|
NA
|
Adverse Events
| Time Frame | AE is reported every 3 weeks for the first 12 weeks, then every 9 weeks for the subsequent 39 weeks, then follow-up up to 5 years after completion of study treatment or until death, whichever occurs first. Median follow-up 3.1 years. The AE data cutoff date is 21 April 2020. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab | ||
| Arm/Group Description | T-DM1 3.6mg/kg every three weeks by IV for 17 doses for a total of 51 weeks | paclitaxel 80 mg/m2 IV weekly and trastuzumab 4 mg/kg IV load, followed by 2 mg/kg IV weekly for 12 weeks, followed by trastuzumab 6 mg/kg IV every 3 weeks for 13 treatments | ||
All Cause Mortality |
||||
| Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/383 (1.6%) | 1/114 (0.9%) | ||
Serious Adverse Events |
||||
| Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 62/383 (16.2%) | 26/114 (22.8%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 4/383 (1%) | 0/114 (0%) | ||
| Febrile neutropenia | 0/383 (0%) | 2/114 (1.8%) | ||
| Leukocytosis | 1/383 (0.3%) | 0/114 (0%) | ||
| Cardiac disorders | ||||
| Left ventricular systolic dysfunction | 1/383 (0.3%) | 0/114 (0%) | ||
| Gastrointestinal disorders | ||||
| Constipation | 1/383 (0.3%) | 0/114 (0%) | ||
| Diarrhea | 2/383 (0.5%) | 3/114 (2.6%) | ||
| Dyspepsia | 1/383 (0.3%) | 0/114 (0%) | ||
| Gastric hemorrhage | 1/383 (0.3%) | 0/114 (0%) | ||
| Nausea | 3/383 (0.8%) | 0/114 (0%) | ||
| Oral hemorrhage | 1/383 (0.3%) | 0/114 (0%) | ||
| Vomiting | 2/383 (0.5%) | 1/114 (0.9%) | ||
| General disorders | ||||
| Fatigue | 3/383 (0.8%) | 2/114 (1.8%) | ||
| Infusion related reaction | 1/383 (0.3%) | 2/114 (1.8%) | ||
| Hepatobiliary disorders | ||||
| Cholecystitis | 1/383 (0.3%) | 0/114 (0%) | ||
| Infections and infestations | ||||
| Gum infection | 1/383 (0.3%) | 0/114 (0%) | ||
| Skin infection | 1/383 (0.3%) | 0/114 (0%) | ||
| Wound infection | 1/383 (0.3%) | 0/114 (0%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 2/383 (0.5%) | 1/114 (0.9%) | ||
| CPK increased | 1/383 (0.3%) | 0/114 (0%) | ||
| Ejection fraction decreased | 0/383 (0%) | 1/114 (0.9%) | ||
| Lipase increased | 1/383 (0.3%) | 0/114 (0%) | ||
| Neutrophil count decreased | 3/383 (0.8%) | 7/114 (6.1%) | ||
| Platelet count decreased | 12/383 (3.1%) | 0/114 (0%) | ||
| Weight loss | 1/383 (0.3%) | 0/114 (0%) | ||
| White blood cell decreased | 1/383 (0.3%) | 1/114 (0.9%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 1/383 (0.3%) | 0/114 (0%) | ||
| Hypernatremia | 0/383 (0%) | 1/114 (0.9%) | ||
| Hypokalemia | 1/383 (0.3%) | 0/114 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 1/383 (0.3%) | 0/114 (0%) | ||
| Myalgia | 1/383 (0.3%) | 0/114 (0%) | ||
| Nervous system disorders | ||||
| Headache | 1/383 (0.3%) | 0/114 (0%) | ||
| Paresthesia | 2/383 (0.5%) | 0/114 (0%) | ||
| Peripheral motor neuropathy | 0/383 (0%) | 4/114 (3.5%) | ||
| Peripheral sensory neuropathy | 9/383 (2.3%) | 6/114 (5.3%) | ||
| Renal and urinary disorders | ||||
| Hematuria | 1/383 (0.3%) | 0/114 (0%) | ||
| Reproductive system and breast disorders | ||||
| Irregular menstruation | 0/383 (0%) | 1/114 (0.9%) | ||
| Menorrhagia | 1/383 (0.3%) | 0/114 (0%) | ||
| Premature menopause | 1/383 (0.3%) | 0/114 (0%) | ||
| Vaginal hemorrhage | 1/383 (0.3%) | 0/114 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 1/383 (0.3%) | 0/114 (0%) | ||
| Dyspnea | 1/383 (0.3%) | 0/114 (0%) | ||
| Epistaxis | 2/383 (0.5%) | 0/114 (0%) | ||
| Pneumonitis | 1/383 (0.3%) | 0/114 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Hyperhidrosis | 1/383 (0.3%) | 0/114 (0%) | ||
| Vascular disorders | ||||
| Hot flashes | 1/383 (0.3%) | 0/114 (0%) | ||
| Hypertension | 8/383 (2.1%) | 2/114 (1.8%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Trastuzumab Emtansine (T-DM1) | Paclitaxel + Trastuzumab | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 383/383 (100%) | 114/114 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 53/383 (13.8%) | 26/114 (22.8%) | ||
| Febrile neutropenia | 0/383 (0%) | 1/114 (0.9%) | ||
| Leukocytosis | 1/383 (0.3%) | 0/114 (0%) | ||
| Lymph node pain | 2/383 (0.5%) | 0/114 (0%) | ||
| Thrombotic thrombocytopenic purpura | 4/383 (1%) | 0/114 (0%) | ||
| Blood and lymphatic system disorders - Other | 9/383 (2.3%) | 2/114 (1.8%) | ||
| Cardiac disorders | ||||
| Atrial fibrillation | 0/383 (0%) | 1/114 (0.9%) | ||
| Chest pain - cardiac | 1/383 (0.3%) | 1/114 (0.9%) | ||
| Left ventricular systolic dysfunction | 1/383 (0.3%) | 0/114 (0%) | ||
| Palpitations | 14/383 (3.7%) | 3/114 (2.6%) | ||
| Pericardial effusion | 1/383 (0.3%) | 1/114 (0.9%) | ||
| Restrictive cardiomyopathy | 0/383 (0%) | 1/114 (0.9%) | ||
| Sinus bradycardia | 1/383 (0.3%) | 3/114 (2.6%) | ||
| Sinus tachycardia | 3/383 (0.8%) | 1/114 (0.9%) | ||
| Supraventricular tachycardia | 1/383 (0.3%) | 0/114 (0%) | ||
| Ventricular arrhythmia | 0/383 (0%) | 1/114 (0.9%) | ||
| Ventricular tachycardia | 1/383 (0.3%) | 0/114 (0%) | ||
| Cardiac disorders - Other | 3/383 (0.8%) | 1/114 (0.9%) | ||
| Ear and labyrinth disorders | ||||
| Ear pain | 4/383 (1%) | 0/114 (0%) | ||
| Hearing impaired | 6/383 (1.6%) | 0/114 (0%) | ||
| Tinnitus | 3/383 (0.8%) | 0/114 (0%) | ||
| Tinnitus | 1/383 (0.3%) | 0/114 (0%) | ||
| Vertigo | 4/383 (1%) | 1/114 (0.9%) | ||
| Vestibular disorder | 1/383 (0.3%) | 0/114 (0%) | ||
| Ear and labyrinth disorders - Other | 1/383 (0.3%) | 0/114 (0%) | ||
| Endocrine disorders | ||||
| Hyperthyroidism | 1/383 (0.3%) | 0/114 (0%) | ||
| Hypothyroidism | 2/383 (0.5%) | 0/114 (0%) | ||
| Endocrine disorders - Other | 2/383 (0.5%) | 0/114 (0%) | ||
| Eye disorders | ||||
| Blurred vision | 25/383 (6.5%) | 6/114 (5.3%) | ||
| Cataract | 2/383 (0.5%) | 0/114 (0%) | ||
| Conjunctivitis | 1/383 (0.3%) | 2/114 (1.8%) | ||
| Dry eye | 44/383 (11.5%) | 5/114 (4.4%) | ||
| Eye pain | 2/383 (0.5%) | 1/114 (0.9%) | ||
| Floaters | 2/383 (0.5%) | 0/114 (0%) | ||
| Retinal detachment | 1/383 (0.3%) | 0/114 (0%) | ||
| Retinal tear | 1/383 (0.3%) | 0/114 (0%) | ||
| Retinal vascular disorder | 0/383 (0%) | 1/114 (0.9%) | ||
| Watering eyes | 12/383 (3.1%) | 3/114 (2.6%) | ||
| Eye disorders - Other | 16/383 (4.2%) | 5/114 (4.4%) | ||
| Gastrointestinal disorders | ||||
| Abdominal distension | 2/383 (0.5%) | 0/114 (0%) | ||
| Abdominal pain | 30/383 (7.8%) | 7/114 (6.1%) | ||
| Bloating | 7/383 (1.8%) | 4/114 (3.5%) | ||
| Cecal hemorrhage | 1/383 (0.3%) | 0/114 (0%) | ||
| Colitis | 1/383 (0.3%) | 1/114 (0.9%) | ||
| Colonic ulcer | 0/383 (0%) | 1/114 (0.9%) | ||
| Constipation | 111/383 (29%) | 12/114 (10.5%) | ||
| Dental caries | 1/383 (0.3%) | 0/114 (0%) | ||
| Diarrhea | 63/383 (16.4%) | 54/114 (47.4%) | ||
| Dry mouth | 118/383 (30.8%) | 6/114 (5.3%) | ||
| Duodenal hemorrhage | 2/383 (0.5%) | 0/114 (0%) | ||
| Duodenal ulcer | 1/383 (0.3%) | 0/114 (0%) | ||
| Dyspepsia | 47/383 (12.3%) | 15/114 (13.2%) | ||
| Dysphagia | 2/383 (0.5%) | 1/114 (0.9%) | ||
| Esophagitis | 2/383 (0.5%) | 0/114 (0%) | ||
| Flatulence | 6/383 (1.6%) | 0/114 (0%) | ||
| Gastritis | 2/383 (0.5%) | 0/114 (0%) | ||
| Gastroesophageal reflux disease | 47/383 (12.3%) | 18/114 (15.8%) | ||
| Gastrointestinal pain | 4/383 (1%) | 2/114 (1.8%) | ||
| Gingival pain | 3/383 (0.8%) | 1/114 (0.9%) | ||
| Hemorrhoidal hemorrhage | 1/383 (0.3%) | 0/114 (0%) | ||
| Hemorrhoids | 6/383 (1.6%) | 2/114 (1.8%) | ||
| Mucositis oral | 48/383 (12.5%) | 15/114 (13.2%) | ||
| Nausea | 192/383 (50.1%) | 46/114 (40.4%) | ||
| Oral dysesthesia | 0/383 (0%) | 2/114 (1.8%) | ||
| Oral hemorrhage | 7/383 (1.8%) | 0/114 (0%) | ||
| Oral pain | 2/383 (0.5%) | 3/114 (2.6%) | ||
| Periodontal disease | 3/383 (0.8%) | 1/114 (0.9%) | ||
| Rectal hemorrhage | 8/383 (2.1%) | 2/114 (1.8%) | ||
| Stomach pain | 4/383 (1%) | 1/114 (0.9%) | ||
| Tooth development disorder | 1/383 (0.3%) | 0/114 (0%) | ||
| Tooth discoloration | 0/383 (0%) | 1/114 (0.9%) | ||
| Toothache | 3/383 (0.8%) | 1/114 (0.9%) | ||
| Vomiting | 38/383 (9.9%) | 13/114 (11.4%) | ||
| Gastrointestinal disorders - Other | 19/383 (5%) | 5/114 (4.4%) | ||
| General disorders | ||||
| Chills | 29/383 (7.6%) | 3/114 (2.6%) | ||
| Edema face | 4/383 (1%) | 3/114 (2.6%) | ||
| Edema limbs | 35/383 (9.1%) | 19/114 (16.7%) | ||
| Edema trunk | 1/383 (0.3%) | 1/114 (0.9%) | ||
| Facial pain | 3/383 (0.8%) | 0/114 (0%) | ||
| Fatigue | 250/383 (65.3%) | 80/114 (70.2%) | ||
| Fever | 39/383 (10.2%) | 9/114 (7.9%) | ||
| Flu like symptoms | 24/383 (6.3%) | 5/114 (4.4%) | ||
| Gait disturbance | 0/383 (0%) | 2/114 (1.8%) | ||
| Infusion related reaction | 23/383 (6%) | 11/114 (9.6%) | ||
| Injection site reaction | 1/383 (0.3%) | 0/114 (0%) | ||
| Irritability | 3/383 (0.8%) | 2/114 (1.8%) | ||
| Localized edema | 11/383 (2.9%) | 4/114 (3.5%) | ||
| Non-cardiac chest pain | 12/383 (3.1%) | 2/114 (1.8%) | ||
| Pain | 46/383 (12%) | 23/114 (20.2%) | ||
| General disorders and administration site conditions - Other | 17/383 (4.4%) | 9/114 (7.9%) | ||
| Hepatobiliary disorders | ||||
| Hepatic pain | 1/383 (0.3%) | 0/114 (0%) | ||
| Hepatobiliary disorders - Other | 7/383 (1.8%) | 1/114 (0.9%) | ||
| Immune system disorders | ||||
| Allergic reaction | 9/383 (2.3%) | 1/114 (0.9%) | ||
| Cytokine release syndrome | 1/383 (0.3%) | 0/114 (0%) | ||
| Immune system disorders - Other | 1/383 (0.3%) | 0/114 (0%) | ||
| Vaginal infection | 1/383 (0.3%) | 1/114 (0.9%) | ||
| Infections and infestations | ||||
| Appendicitis | 1/383 (0.3%) | 0/114 (0%) | ||
| Bladder infection | 1/383 (0.3%) | 0/114 (0%) | ||
| Breast infection | 5/383 (1.3%) | 2/114 (1.8%) | ||
| Bronchial infection | 2/383 (0.5%) | 1/114 (0.9%) | ||
| Catheter related infection | 1/383 (0.3%) | 1/114 (0.9%) | ||
| Conjunctivitis infective | 2/383 (0.5%) | 0/114 (0%) | ||
| Esophageal infection | 1/383 (0.3%) | 0/114 (0%) | ||
| Eye infection | 1/383 (0.3%) | 2/114 (1.8%) | ||
| Gum infection | 1/383 (0.3%) | 0/114 (0%) | ||
| Laryngitis | 1/383 (0.3%) | 0/114 (0%) | ||
| Laryngitis | 2/383 (0.5%) | 0/114 (0%) | ||
| Lip infection | 1/383 (0.3%) | 0/114 (0%) | ||
| Lip infection | 2/383 (0.5%) | 0/114 (0%) | ||
| Lung infection | 5/383 (1.3%) | 1/114 (0.9%) | ||
| Mucosal infection | 2/383 (0.5%) | 1/114 (0.9%) | ||
| Nail infection | 2/383 (0.5%) | 1/114 (0.9%) | ||
| Otitis externa | 3/383 (0.8%) | 0/114 (0%) | ||
| Otitis media | 7/383 (1.8%) | 1/114 (0.9%) | ||
| Papulopustular rash | 7/383 (1.8%) | 5/114 (4.4%) | ||
| Paronychia | 3/383 (0.8%) | 0/114 (0%) | ||
| Pharyngitis | 2/383 (0.5%) | 1/114 (0.9%) | ||
| Phlebitis infective | 0/383 (0%) | 1/114 (0.9%) | ||
| Rash pustular | 1/383 (0.3%) | 0/114 (0%) | ||
| Rhinitis infective | 4/383 (1%) | 0/114 (0%) | ||
| Rhinitis infective | 1/383 (0.3%) | 0/114 (0%) | ||
| Sepsis | 0/383 (0%) | 1/114 (0.9%) | ||
| Sinusitis | 15/383 (3.9%) | 1/114 (0.9%) | ||
| Sinusitis | 15/383 (3.9%) | 3/114 (2.6%) | ||
| Skin infection | 4/383 (1%) | 2/114 (1.8%) | ||
| Skin infection | 12/383 (3.1%) | 7/114 (6.1%) | ||
| Soft tissue infection | 1/383 (0.3%) | 0/114 (0%) | ||
| Stoma site infection | 1/383 (0.3%) | 0/114 (0%) | ||
| Tooth infection | 4/383 (1%) | 2/114 (1.8%) | ||
| Upper respiratory infection | 13/383 (3.4%) | 2/114 (1.8%) | ||
| Upper respiratory infection | 28/383 (7.3%) | 9/114 (7.9%) | ||
| Urinary tract infection | 2/383 (0.5%) | 3/114 (2.6%) | ||
| Urinary tract infection | 34/383 (8.9%) | 3/114 (2.6%) | ||
| Vaginal infection | 6/383 (1.6%) | 2/114 (1.8%) | ||
| Wound infection | 2/383 (0.5%) | 0/114 (0%) | ||
| Infections and infestations - Other | 13/383 (3.4%) | 10/114 (8.8%) | ||
| Ankle fracture | 1/383 (0.3%) | 0/114 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| Bruising | 15/383 (3.9%) | 0/114 (0%) | ||
| Burn | 5/383 (1.3%) | 1/114 (0.9%) | ||
| Dermatitis radiation | 44/383 (11.5%) | 13/114 (11.4%) | ||
| Fall | 5/383 (1.3%) | 5/114 (4.4%) | ||
| Fracture | 1/383 (0.3%) | 3/114 (2.6%) | ||
| Intraoperative breast injury | 0/383 (0%) | 1/114 (0.9%) | ||
| Intraoperative skin injury | 0/383 (0%) | 1/114 (0.9%) | ||
| Radiation recall reaction (dermatologic) | 1/383 (0.3%) | 0/114 (0%) | ||
| Seroma | 3/383 (0.8%) | 1/114 (0.9%) | ||
| Spinal fracture | 1/383 (0.3%) | 0/114 (0%) | ||
| Vascular access complication | 1/383 (0.3%) | 0/114 (0%) | ||
| Wound complication | 1/383 (0.3%) | 1/114 (0.9%) | ||
| Wrist fracture | 1/383 (0.3%) | 0/114 (0%) | ||
| Injury, poisoning and procedural complications - Other, specify | 5/383 (1.3%) | 1/114 (0.9%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 111/383 (29%) | 18/114 (15.8%) | ||
| Alkaline phosphatase increased | 57/383 (14.9%) | 2/114 (1.8%) | ||
| Aspartate aminotransferase increased | 129/383 (33.7%) | 9/114 (7.9%) | ||
| Blood bilirubin increased | 38/383 (9.9%) | 4/114 (3.5%) | ||
| Creatinine increased | 4/383 (1%) | 5/114 (4.4%) | ||
| Ejection fraction decreased | 3/383 (0.8%) | 2/114 (1.8%) | ||
| Lipase increased | 2/383 (0.5%) | 0/114 (0%) | ||
| Lymphocyte count decreased | 14/383 (3.7%) | 4/114 (3.5%) | ||
| Lymphocyte count increased | 1/383 (0.3%) | 0/114 (0%) | ||
| Neutrophil count decreased | 24/383 (6.3%) | 18/114 (15.8%) | ||
| Platelet count decreased | 89/383 (23.2%) | 5/114 (4.4%) | ||
| Weight gain | 8/383 (2.1%) | 6/114 (5.3%) | ||
| Weight loss | 28/383 (7.3%) | 6/114 (5.3%) | ||
| White blood cell decreased | 24/383 (6.3%) | 14/114 (12.3%) | ||
| Investigations - Other, specify | 9/383 (2.3%) | 3/114 (2.6%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 58/383 (15.1%) | 14/114 (12.3%) | ||
| Dehydration | 10/383 (2.6%) | 4/114 (3.5%) | ||
| Glucose intolerance | 3/383 (0.8%) | 0/114 (0%) | ||
| Hypercalcemia | 9/383 (2.3%) | 0/114 (0%) | ||
| Hyperglycemia | 28/383 (7.3%) | 6/114 (5.3%) | ||
| Hyperkalemia | 5/383 (1.3%) | 1/114 (0.9%) | ||
| Hypernatremia | 3/383 (0.8%) | 2/114 (1.8%) | ||
| Hypertriglyceridemia | 1/383 (0.3%) | 0/114 (0%) | ||
| Hypoalbuminemia | 19/383 (5%) | 5/114 (4.4%) | ||
| Hypocalcemia | 3/383 (0.8%) | 5/114 (4.4%) | ||
| Hypoglycemia | 9/383 (2.3%) | 1/114 (0.9%) | ||
| Hypokalemia | 2/383 (0.5%) | 4/114 (3.5%) | ||
| Hypokalemia | 32/383 (8.4%) | 4/114 (3.5%) | ||
| Hypomagnesemia | 2/383 (0.5%) | 1/114 (0.9%) | ||
| Hyponatremia | 11/383 (2.9%) | 4/114 (3.5%) | ||
| Hypophosphatemia | 1/383 (0.3%) | 0/114 (0%) | ||
| Metabolism and nutrition disorders - Other | 3/383 (0.8%) | 0/114 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 94/383 (24.5%) | 28/114 (24.6%) | ||
| Arthritis | 7/383 (1.8%) | 3/114 (2.6%) | ||
| Back pain | 29/383 (7.6%) | 12/114 (10.5%) | ||
| Bone pain | 13/383 (3.4%) | 6/114 (5.3%) | ||
| Chest wall pain | 5/383 (1.3%) | 3/114 (2.6%) | ||
| Fibrosis deep connective tissue | 1/383 (0.3%) | 0/114 (0%) | ||
| Flank pain | 5/383 (1.3%) | 1/114 (0.9%) | ||
| Generalized muscle weakness | 9/383 (2.3%) | 6/114 (5.3%) | ||
| Growth suppression | 1/383 (0.3%) | 0/114 (0%) | ||
| Joint range of motion decreased | 8/383 (2.1%) | 1/114 (0.9%) | ||
| Muscle weakness lower limb | 1/383 (0.3%) | 2/114 (1.8%) | ||
| Muscle weakness upper limb | 2/383 (0.5%) | 0/114 (0%) | ||
| Myalgia | 75/383 (19.6%) | 15/114 (13.2%) | ||
| Neck pain | 11/383 (2.9%) | 0/114 (0%) | ||
| Osteoporosis | 6/383 (1.6%) | 1/114 (0.9%) | ||
| Pain in extremity | 34/383 (8.9%) | 14/114 (12.3%) | ||
| Superficial soft tissue fibrosis | 1/383 (0.3%) | 1/114 (0.9%) | ||
| Musculoskeletal and connective tissue disorder - Other, specify | 29/383 (7.6%) | 5/114 (4.4%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other | 4/383 (1%) | 0/114 (0%) | ||
| Nervous system disorders | ||||
| Akathisia | 2/383 (0.5%) | 2/114 (1.8%) | ||
| Amnesia | 1/383 (0.3%) | 0/114 (0%) | ||
| Ataxia | 1/383 (0.3%) | 0/114 (0%) | ||
| Cognitive disturbance | 4/383 (1%) | 1/114 (0.9%) | ||
| Concentration impairment | 4/383 (1%) | 1/114 (0.9%) | ||
| Dizziness | 28/383 (7.3%) | 15/114 (13.2%) | ||
| Dysgeusia | 55/383 (14.4%) | 11/114 (9.6%) | ||
| Dysphasia | 0/383 (0%) | 1/114 (0.9%) | ||
| Extrapyramidal disorder | 1/383 (0.3%) | 0/114 (0%) | ||
| Headache | 118/383 (30.8%) | 33/114 (28.9%) | ||
| Hypersomnia | 2/383 (0.5%) | 0/114 (0%) | ||
| Lethargy | 1/383 (0.3%) | 0/114 (0%) | ||
| Leukoencephalopathy | 0/383 (0%) | 1/114 (0.9%) | ||
| Memory impairment | 8/383 (2.1%) | 4/114 (3.5%) | ||
| Paresthesia | 28/383 (7.3%) | 7/114 (6.1%) | ||
| Peripheral motor neuropathy | 23/383 (6%) | 17/114 (14.9%) | ||
| Peripheral sensory neuropathy | 119/383 (31.1%) | 50/114 (43.9%) | ||
| Presyncope | 3/383 (0.8%) | 1/114 (0.9%) | ||
| Sinus pain | 1/383 (0.3%) | 1/114 (0.9%) | ||
| Spasticity | 1/383 (0.3%) | 1/114 (0.9%) | ||
| Syncope | 1/383 (0.3%) | 1/114 (0.9%) | ||
| Tremor | 2/383 (0.5%) | 1/114 (0.9%) | ||
| Nervous system disorders - Other | 7/383 (1.8%) | 6/114 (5.3%) | ||
| Psychiatric disorders | ||||
| Agitation | 4/383 (1%) | 0/114 (0%) | ||
| Anxiety | 38/383 (9.9%) | 23/114 (20.2%) | ||
| Confusion | 1/383 (0.3%) | 0/114 (0%) | ||
| Depression | 34/383 (8.9%) | 8/114 (7%) | ||
| Hallucinations | 1/383 (0.3%) | 0/114 (0%) | ||
| Insomnia | 58/383 (15.1%) | 30/114 (26.3%) | ||
| Libido decreased | 3/383 (0.8%) | 2/114 (1.8%) | ||
| Restlessness | 2/383 (0.5%) | 0/114 (0%) | ||
| Psychiatric disorders - Other | 3/383 (0.8%) | 4/114 (3.5%) | ||
| Renal and urinary disorders | ||||
| Acute kidney injury | 1/383 (0.3%) | 0/114 (0%) | ||
| Hematuria | 5/383 (1.3%) | 0/114 (0%) | ||
| Proteinuria | 1/383 (0.3%) | 0/114 (0%) | ||
| Renal calculi | 1/383 (0.3%) | 0/114 (0%) | ||
| Urinary frequency | 7/383 (1.8%) | 2/114 (1.8%) | ||
| Urinary incontinence | 3/383 (0.8%) | 1/114 (0.9%) | ||
| Urinary retention | 1/383 (0.3%) | 0/114 (0%) | ||
| Urinary tract pain | 8/383 (2.1%) | 0/114 (0%) | ||
| Urinary urgency | 3/383 (0.8%) | 0/114 (0%) | ||
| Renal and urinary disorders - Other | 2/383 (0.5%) | 0/114 (0%) | ||
| Reproductive system and breast disorders | ||||
| Breast pain | 31/383 (8.1%) | 7/114 (6.1%) | ||
| Dysmenorrhea | 1/383 (0.3%) | 0/114 (0%) | ||
| Dyspareunia | 2/383 (0.5%) | 0/114 (0%) | ||
| Genital edema | 0/383 (0%) | 1/114 (0.9%) | ||
| Irregular menstruation | 13/383 (3.4%) | 2/114 (1.8%) | ||
| Menorrhagia | 9/383 (2.3%) | 1/114 (0.9%) | ||
| Ovarian rupture | 1/383 (0.3%) | 0/114 (0%) | ||
| Pelvic pain | 2/383 (0.5%) | 0/114 (0%) | ||
| Uterine hemorrhage | 0/383 (0%) | 1/114 (0.9%) | ||
| Vaginal discharge | 4/383 (1%) | 0/114 (0%) | ||
| Vaginal dryness | 18/383 (4.7%) | 8/114 (7%) | ||
| Vaginal hemorrhage | 2/383 (0.5%) | 0/114 (0%) | ||
| Vaginal pain | 1/383 (0.3%) | 1/114 (0.9%) | ||
| Vaginal stricture | 0/383 (0%) | 1/114 (0.9%) | ||
| Reproductive system and breast disorders - Other | 14/383 (3.7%) | 2/114 (1.8%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Allergic rhinitis | 21/383 (5.5%) | 4/114 (3.5%) | ||
| Cough | 56/383 (14.6%) | 21/114 (18.4%) | ||
| Dyspnea | 27/383 (7%) | 8/114 (7%) | ||
| Epistaxis | 90/383 (23.5%) | 25/114 (21.9%) | ||
| Laryngeal inflammation | 1/383 (0.3%) | 1/114 (0.9%) | ||
| Nasal congestion | 45/383 (11.7%) | 10/114 (8.8%) | ||
| Pleural effusion | 1/383 (0.3%) | 1/114 (0.9%) | ||
| Pneumonitis | 6/383 (1.6%) | 3/114 (2.6%) | ||
| Postnasal drip | 15/383 (3.9%) | 2/114 (1.8%) | ||
| Productive cough | 5/383 (1.3%) | 0/114 (0%) | ||
| Pulmonary hypertension | 3/383 (0.8%) | 0/114 (0%) | ||
| Sinus disorder | 4/383 (1%) | 0/114 (0%) | ||
| Sleep apnea | 1/383 (0.3%) | 0/114 (0%) | ||
| Sore throat | 21/383 (5.5%) | 8/114 (7%) | ||
| Tracheal fistula | 4/383 (1%) | 1/114 (0.9%) | ||
| Voice alteration | 2/383 (0.5%) | 0/114 (0%) | ||
| Wheezing | 0/383 (0%) | 2/114 (1.8%) | ||
| Respiratory, thoracic and mediastinal disorders - Other | 17/383 (4.4%) | 6/114 (5.3%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 21/383 (5.5%) | 64/114 (56.1%) | ||
| Bullous dermatitis | 1/383 (0.3%) | 0/114 (0%) | ||
| Dry skin | 29/383 (7.6%) | 15/114 (13.2%) | ||
| Erythema multiforme | 3/383 (0.8%) | 0/114 (0%) | ||
| Erythema multiforme | 4/383 (1%) | 0/114 (0%) | ||
| Erythroderma | 3/383 (0.8%) | 0/114 (0%) | ||
| Hyperhidrosis | 3/383 (0.8%) | 2/114 (1.8%) | ||
| Hypohidrosis | 1/383 (0.3%) | 0/114 (0%) | ||
| Nail discoloration | 4/383 (1%) | 14/114 (12.3%) | ||
| Nail loss | 4/383 (1%) | 5/114 (4.4%) | ||
| Nail ridging | 6/383 (1.6%) | 3/114 (2.6%) | ||
| Pain of skin | 2/383 (0.5%) | 2/114 (1.8%) | ||
| Palmar-plantar erythrodysesthesia syndrome | 0/383 (0%) | 2/114 (1.8%) | ||
| Periorbital edema | 1/383 (0.3%) | 0/114 (0%) | ||
| Photosensitivity | 1/383 (0.3%) | 1/114 (0.9%) | ||
| Pruritus | 18/383 (4.7%) | 10/114 (8.8%) | ||
| Rash acneiform | 30/383 (7.8%) | 16/114 (14%) | ||
| Rash maculo-papular | 39/383 (10.2%) | 17/114 (14.9%) | ||
| Scalp pain | 1/383 (0.3%) | 4/114 (3.5%) | ||
| Skin hyperpigmentation | 10/383 (2.6%) | 3/114 (2.6%) | ||
| Skin ulceration | 2/383 (0.5%) | 1/114 (0.9%) | ||
| Telangiectasia | 3/383 (0.8%) | 1/114 (0.9%) | ||
| Urticaria | 2/383 (0.5%) | 1/114 (0.9%) | ||
| Skin and subcutaneous tissue disorders - Other | 53/383 (13.8%) | 20/114 (17.5%) | ||
| Vascular disorders | ||||
| Flushing | 4/383 (1%) | 6/114 (5.3%) | ||
| Hematoma | 3/383 (0.8%) | 0/114 (0%) | ||
| Hot flashes | 60/383 (15.7%) | 34/114 (29.8%) | ||
| Hypertension | 78/383 (20.4%) | 29/114 (25.4%) | ||
| Hypotension | 2/383 (0.5%) | 1/114 (0.9%) | ||
| Lymphedema | 8/383 (2.1%) | 5/114 (4.4%) | ||
| Phlebitis | 1/383 (0.3%) | 0/114 (0%) | ||
| Thromboembolic event | 1/383 (0.3%) | 0/114 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Sara Tolaney, MD, MPH |
|---|---|
| Organization | Dana-Farber Cancer Institute |
| Phone | (877) 442-3324 |
| Sara_Tolaney@dfci.harvard.edu |
- 13-048