Eribulin in HER2 Negative Metastatic BrCa
Study Details
Study Description
Brief Summary
Improvements in outcomes with metastatic breast cancer (MBC) have been observed in the last 30 years, however, overall prognosis remains poor with median survival of 2 to 3 years. Long term complete responses are observed only for a minority of MBC patients (2-5%) and MBC remains an incurable disease for most patients. Eribulin is a chemotherapy approved by the US FDA in November of 2010 to treat patients with MBC who have received at least two prior chemotherapy regimens. In this research study, the investigators are looking to see how well eribulin helps participants with MBC in an earlier-line setting. Eribulin works by interfering with cancer cell division, growth and spread.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
Based on positive results in heavily pre-treated MBC patients, eribulin is being studied as first-line or second-line chemotherapy treatment. This is a non-randomized, open label study with participants enrolled in one of two cohorts: Cohort 1. Hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) or Cohort 2: Triple negative breast cancer (TNBC) meaning HR-negative/HER2-negative (HR-/HER2-). HR- means progesterone receptor-negative (PR-) and estrogen receptor-negative (ER-). Beyond efficacy as measured primarily by response to treatment, investigators will evaluate safety, tolerability and quality of life. In particular, it is hypothesized that eribulin may have lower rates of neuropathy, a common side effect of many of the major chemotherapeutics with activity in MBC. The investigators will study the effect eribulin has on the nerves through regular questionnaires that ask about any nerve-related symptoms. The investigators also plan to send blood samples to explore if gene markers may indicate increased sensitivity to the nerve effects of eribulin.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1: HR+/HER2- Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. |
Drug: Eribulin
Other Names:
|
| Experimental: Cohort 2: TNBC Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. |
Drug: Eribulin
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Response Rate (ORR) [Disease was evaluated radiologically at baseline and every 9 weeks on treatment; Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2)]
ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Secondary Outcome Measures
- Progression-Free Survival (PFS) [Disease was evaluated radiologically at baseline and every 9 weeks on and off treatment; Median (maximum) PFS follow-up was 12.6 (27.1) months in Cohort 1 and 12.4 (14.3) months in Cohort 2.]
PFS based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Participants alive without PD are censored at date of last disease assessment. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum longest diameter (LD), taking as reference the smallest sum on study with at least 5 mm absolute increase or the appearance of one or more new lesions. For non-target lesions, PD is appearance of one or more new lesions or unequivocal progression of existing non-target lesions.
- Time to First Response (TTR) [Disease was evaluated radiologically at baseline and every 9 weeks on treatment; Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2).]
TTR is defined as the time from first dose of study treatment until the earliest date that complete response (CR) or partial response (PR) based on RECIST 1.1 criteria is objectively documented. Non-CR, non-PR participants are censored at date of last disease assessment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response requires 4 week or later confirmation and assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
- Duration of Overall Response (DOR) [Disease was evaluated radiologically at baseline and every 9 weeks on and off treatment; Median (maximum) DOR follow-up was 12.6 (27.1) months in Cohort 1 and 12.4 (14.3) months in Cohort 2.]
DOR is defined as the that response criteria for CR or PR (whichever is recorded first) are first met until the date that PD or death from any cause is first objectively documented. Participants who do not have PD will be censored on date of last disease assessment.
- Percentage of Participants With Grade 1-3 Treatment-Related Peripheral Sensory Neuropathy [Adverse events were assessed every cycle throughout treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2)]
The percentage of treated participants experiencing grade 1-3 peripheral sensory neuropathy with treatment attribution of possible, probable or definite based on Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) as reported on case report forms.
- Percentage of Participants With Grade 1-3 Treatment-Related Peripheral Motor Neuropathy [Adverse events were assessed every cycle throughout treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2)]
TThe percentage of treated participants experiencing grade 1-3 peripheral motor neuropathy with treatment attribution of possible, probable or definite based on Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) as reported on case report forms.
- Functional Assessment of Cancer Therapy-Breast Cancer Subscale (FACT-BCS) Change Score From Baseline [Assessed at baseline and on treatment day 1 of cycles 2, 3, 5, 7, 9 and 11]
The FACT-BCS is a validated, self-administered questionnaire which captures quality of life (QOL) concerns specific to breast cancer patients. (Brady MJ, et al. Reliability and validity of the Functional Assessment of Cancer Therapy-Breast quality-of-life instrument. JCO 1997; 15:974-86). The FACT-BCS has 9-items scored on a 5-point Likert scale (Not at all, A little bit, Somewhat, Quite a bit, Very much) with a maximum score of 36. A higher score indicates better QOL. A minimal clinically important difference is 3-5 points.
- Functional Assessment of Cancer Therapy-Neurotoxicity Subscale (FACT-Ntx) Change Score From Baseline [Assessed at baseline and on treatment day 1 of cycles 2, 3, 5, 7, 9 and 11]
The FACT-Ntx is a validated, self-administered questionnaire which captures quality of life (QOL) concerns specific to patients suffering from neurotoxicity. (Calhoun EA, et al. Psychometric evaluation of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire for patients receiving systemic chemotherapy. Int J Gynecol Cancer 2003; 13:741-8). The FACT-Ntx has 11-items scored on a 5-point Likert scale (Not at all, A little bit, Somewhat, Quite a bit, Very much) with a maximum score of 44. A higher score indicates better QOL. A minimal clinically important difference is 3-5 points.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Histologically or cytologically proven invasive breast cancer, locally recurrent or metastatic, with at least one measureable lesion according to RECIST v1.1
-
Hormone receptor positive or hormone receptor negative HER2-negative disease
-
Up to one prior line of chemotherapy for advanced disease is allowed (discontinued at least 14 days prior to initiation of protocol therapy)
-
Prior bevacizumab in the neo/adjuvant or metastatic setting is acceptable
-
No limit on prior lines of endocrine therapy, but must be discontinued at least 7 days prior to initiation of protocol therapy
-
Must have completed any prior radiotherapy at least 2 weeks prior to initiation of protocol therapy
-
Must have recovered from reversible effects of prior therapies to no more than grade 1 toxicity, with the exception of alopecia
-
Agree to use adequate contraception for the duration of study participation
Exclusion Criteria:
-
Pregnant or breastfeeding
-
Prior treatment with eribulin
-
Prior malignancy other than carcinoma in situ of the cervix or nonmelanoma skin cancer unless diagnosed and definitively treated at least 3 years before enrollment in this study
-
Clinically significant cardiovascular impairment
-
Active brain metastases or unevaluated neurologic symptoms suggestive of brain metastases
-
Pulmonary dysfunction requiring the use of oxygen
-
Prior organ allograft requiring immunosuppression
-
HIV positive on combination antiretroviral therapy
-
Pre-existing grade 3 or 4 neuropathy
-
Hypersensitivity to halichondrin B or halichondrin B chemical derivative
-
Uncontrolled intercurrent illness
-
Inability to read in English
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Eastern Maine Medical Center | Bangor | Maine | United States | 04402 |
| 2 | Dana-Farber Cancer Institute at Faulkner Hospital | Boston | Massachusetts | United States | 02130 |
| 3 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
| 4 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 5 | DF/BWCC at Milford Regional Cancer Center | Milford | Massachusetts | United States | 01757 |
| 6 | South Shore Hospital | Weymouth | Massachusetts | United States | 02190 |
| 7 | Dana-Farber/New Hampshire Oncology-Hematology | Londonderry | New Hampshire | United States | 03053 |
Sponsors and Collaborators
- Dana-Farber Cancer Institute
Investigators
- Principal Investigator: Erica Mayer, MD, MPH, Dana-Farber Cancer Institute
Study Documents (Full-Text)
More Information
Publications
None provided.- 13-077
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled between May 2013 and March 2016. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Cohort 1: HR+/HER2- | Cohort 2: TNBC |
|---|---|---|
| Arm/Group Description | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. |
| Period Title: Overall Study | ||
| STARTED | 45 | 38 |
| COMPLETED | 45 | 38 |
| NOT COMPLETED | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Cohort 1: HR+/HER2- | Cohort 2: TNBC | Total |
|---|---|---|---|
| Arm/Group Description | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. | Total of all reporting groups |
| Overall Participants | 45 | 38 | 83 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
35
77.8%
|
33
86.8%
|
68
81.9%
|
| >=65 years |
10
22.2%
|
5
13.2%
|
15
18.1%
|
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
59
|
53
|
56
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
45
100%
|
38
100%
|
83
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
41
91.1%
|
35
92.1%
|
76
91.6%
|
| Not Hispanic or Latino |
1
2.2%
|
1
2.6%
|
2
2.4%
|
| Unknown or Not Reported |
3
6.7%
|
2
5.3%
|
5
6%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
3
7.9%
|
3
3.6%
|
| White |
42
93.3%
|
34
89.5%
|
76
91.6%
|
| More than one race |
1
2.2%
|
0
0%
|
1
1.2%
|
| Unknown or Not Reported |
2
4.4%
|
1
2.6%
|
3
3.6%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
45
100%
|
38
100%
|
83
100%
|
| Eastern Cooperative Oncology Group Performance Score (ECOG PS) (Count of Participants) | |||
| ECOG PS0 |
33
73.3%
|
26
68.4%
|
59
71.1%
|
| ECOG PS1 |
11
24.4%
|
12
31.6%
|
23
27.7%
|
| ECOG PS2 |
1
2.2%
|
0
0%
|
1
1.2%
|
Outcome Measures
| Title | Overall Response Rate (ORR) |
|---|---|
| Description | ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. |
| Time Frame | Disease was evaluated radiologically at baseline and every 9 weeks on treatment; Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Cohort 1: HR+/HER2- | Cohort 2: TNBC |
|---|---|---|
| Arm/Group Description | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. |
| Measure Participants | 45 | 38 |
| Number (90% Confidence Interval) [percentage of participants] |
35.6
79.1%
|
13.2
34.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Cohort 1: HR+/HER2- |
|---|---|---|
| Comments | Using a one sample binomial design, with 45 patients there was 90% power to detect a null hypothesis 30% overall response rate (historical control) versus an alternative hypothesis of 53% overall response rate assuming a two-sided 10% alpha. Of note, cohort 2: TNBC did not fully accrue 45 patients so a testing was not done. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.42 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Progression-Free Survival (PFS) |
|---|---|
| Description | PFS based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Participants alive without PD are censored at date of last disease assessment. Per RECIST 1.1 for target lesions: PD is at least a 20% increase in sum longest diameter (LD), taking as reference the smallest sum on study with at least 5 mm absolute increase or the appearance of one or more new lesions. For non-target lesions, PD is appearance of one or more new lesions or unequivocal progression of existing non-target lesions. |
| Time Frame | Disease was evaluated radiologically at baseline and every 9 weeks on and off treatment; Median (maximum) PFS follow-up was 12.6 (27.1) months in Cohort 1 and 12.4 (14.3) months in Cohort 2. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis dataset is comprised of all enrolled participants. |
| Arm/Group Title | Cohort 1: HR+/HER2- | Cohort 2: TNBC |
|---|---|---|
| Arm/Group Description | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. |
| Measure Participants | 45 | 38 |
| Mean (90% Confidence Interval) [months] |
6.2
|
4.0
|
| Title | Time to First Response (TTR) |
|---|---|
| Description | TTR is defined as the time from first dose of study treatment until the earliest date that complete response (CR) or partial response (PR) based on RECIST 1.1 criteria is objectively documented. Non-CR, non-PR participants are censored at date of last disease assessment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response requires 4 week or later confirmation and assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. |
| Time Frame | Disease was evaluated radiologically at baseline and every 9 weeks on treatment; Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis dataset is comprised of all enrolled participants. |
| Arm/Group Title | Cohort 1: HR+/HER2- | Cohort 2: TNBC |
|---|---|---|
| Arm/Group Description | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. |
| Measure Participants | 45 | 38 |
| Median (Full Range) [months] |
10.6
|
NA
|
| Title | Duration of Overall Response (DOR) |
|---|---|
| Description | DOR is defined as the that response criteria for CR or PR (whichever is recorded first) are first met until the date that PD or death from any cause is first objectively documented. Participants who do not have PD will be censored on date of last disease assessment. |
| Time Frame | Disease was evaluated radiologically at baseline and every 9 weeks on and off treatment; Median (maximum) DOR follow-up was 12.6 (27.1) months in Cohort 1 and 12.4 (14.3) months in Cohort 2. |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis dataset is comprised of all enrolled participants. |
| Arm/Group Title | Cohort 1: HR+/HER2- | Cohort 2: TNBC |
|---|---|---|
| Arm/Group Description | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. |
| Measure Participants | 45 | 38 |
| Median (Full Range) [months] |
6.5
|
1.9
|
| Title | Percentage of Participants With Grade 1-3 Treatment-Related Peripheral Sensory Neuropathy |
|---|---|
| Description | The percentage of treated participants experiencing grade 1-3 peripheral sensory neuropathy with treatment attribution of possible, probable or definite based on Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) as reported on case report forms. |
| Time Frame | Adverse events were assessed every cycle throughout treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis dataset is comprised of all treated participants. Per protocol, the cohorts were combined for this analysis. |
| Arm/Group Title | Combined Cohort 1: HR+/HER2- and Cohort 2: TNBC |
|---|---|
| Arm/Group Description | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. |
| Measure Participants | 83 |
| Number (90% Confidence Interval) [percentage of participants] |
36.1
80.2%
|
| Title | Percentage of Participants With Grade 1-3 Treatment-Related Peripheral Motor Neuropathy |
|---|---|
| Description | TThe percentage of treated participants experiencing grade 1-3 peripheral motor neuropathy with treatment attribution of possible, probable or definite based on Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) as reported on case report forms. |
| Time Frame | Adverse events were assessed every cycle throughout treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis dataset is comprised of all treated participants.Per protocol, the cohorts were combined for this analysis. |
| Arm/Group Title | Combined Cohort 1: HR+/HER2- and Cohort 2: TNBC |
|---|---|
| Arm/Group Description | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. |
| Measure Participants | 83 |
| Number (90% Confidence Interval) [percentage of participants] |
22.9
50.9%
|
| Title | Functional Assessment of Cancer Therapy-Breast Cancer Subscale (FACT-BCS) Change Score From Baseline |
|---|---|
| Description | The FACT-BCS is a validated, self-administered questionnaire which captures quality of life (QOL) concerns specific to breast cancer patients. (Brady MJ, et al. Reliability and validity of the Functional Assessment of Cancer Therapy-Breast quality-of-life instrument. JCO 1997; 15:974-86). The FACT-BCS has 9-items scored on a 5-point Likert scale (Not at all, A little bit, Somewhat, Quite a bit, Very much) with a maximum score of 36. A higher score indicates better QOL. A minimal clinically important difference is 3-5 points. |
| Time Frame | Assessed at baseline and on treatment day 1 of cycles 2, 3, 5, 7, 9 and 11 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis dataset is comprised of all participants who completed both QOL assessments required to calculate change from baseline. Per protocol, the cohorts were combined for this analysis. |
| Arm/Group Title | Combined Group (Hormone Receptor Positive and Triple Negative) |
|---|---|
| Arm/Group Description | Eribulin Monotherapy Eribulin: Intravenously on Day 1 and 8 of each cycle |
| Measure Participants | 83 |
| Cycle 2 Change from Baseline |
1.0
(4.6)
|
| Cycle 3 Change from Baseline |
0.6
(5.1)
|
| Cycle 5 Change from Baseline |
0.1
(4.4)
|
| Cycle 7 Change from Baseline |
0.6
(3.2)
|
| Cycle 9 Change from Baseline |
1.8
(5.0)
|
| Cycle 11 Change from Baseline |
1.1
(2.9)
|
| Title | Functional Assessment of Cancer Therapy-Neurotoxicity Subscale (FACT-Ntx) Change Score From Baseline |
|---|---|
| Description | The FACT-Ntx is a validated, self-administered questionnaire which captures quality of life (QOL) concerns specific to patients suffering from neurotoxicity. (Calhoun EA, et al. Psychometric evaluation of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire for patients receiving systemic chemotherapy. Int J Gynecol Cancer 2003; 13:741-8). The FACT-Ntx has 11-items scored on a 5-point Likert scale (Not at all, A little bit, Somewhat, Quite a bit, Very much) with a maximum score of 44. A higher score indicates better QOL. A minimal clinically important difference is 3-5 points. |
| Time Frame | Assessed at baseline and on treatment day 1 of cycles 2, 3, 5, 7, 9 and 11 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis dataset is comprised of all participants who completed both QOL assessments required to calculate change from baseline. Per protocol, the cohorts were combined for this analysis. |
| Arm/Group Title | Combine Cohort 1: HR+/HER2- and Cohort 2: TNBC |
|---|---|
| Arm/Group Description | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. |
| Measure Participants | 83 |
| Cycle 2 Change from Baseline |
-0.1
(3.0)
|
| Cycle 3 Change from Baseline |
-0.3
(4.7)
|
| Cycle 5 Change from Baseline |
-1.6
(5.5)
|
| Cycle 7 Change from Baseline |
-4.5
(6.4)
|
| Cycle 9 Change from Baseline |
-1.8
(5.9)
|
| Cycle 11 Change from Baseline |
-1.6
(4.7)
|
| Title | Overall Survival |
|---|---|
| Description | OS based on Kaplan-Meier is defined as the time from study entry to death or censored at date last known alive. |
| Time Frame | Overall median survival follow-up was 5.9 months including a maximum of 27 months for Cohort 1 and 15 months for Cohort 2. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Cohort 1: HR+/HER2- | Cohort 2: TNBC |
|---|---|---|
| Arm/Group Description | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. |
| Measure Participants | 45 | 38 |
| Median (90% Confidence Interval) [months] |
20
|
11.3
|
Adverse Events
| Time Frame | Adverse events (AEs) were assessed every cycle on treatment. Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2). | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment attribution of possibly, probably or definitely and grade 3 or higher. All remaining events regardless of treatment attribution were classified as Other AEs. No further data is available to specify classification of other beyond the general term. | |||
| Arm/Group Title | Cohort 1: HR+/HER2- | Cohort 2: TNBC | ||
| Arm/Group Description | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. | Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle Participants remained on single agent eribulin until disease progression or withdrawal for other reasons. | ||
All Cause Mortality |
||||
| Cohort 1: HR+/HER2- | Cohort 2: TNBC | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/45 (8.9%) | 9/38 (23.7%) | ||
Serious Adverse Events |
||||
| Cohort 1: HR+/HER2- | Cohort 2: TNBC | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 22/45 (48.9%) | 13/38 (34.2%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 0/45 (0%) | 2/38 (5.3%) | ||
| Febrile neutropenia | 2/45 (4.4%) | 2/38 (5.3%) | ||
| Gastrointestinal disorders | ||||
| Diarrhea | 1/45 (2.2%) | 1/38 (2.6%) | ||
| Mucositis oral | 1/45 (2.2%) | 0/38 (0%) | ||
| Nausea | 0/45 (0%) | 1/38 (2.6%) | ||
| Vomiting | 1/45 (2.2%) | 2/38 (5.3%) | ||
| General disorders | ||||
| Fatigue | 1/45 (2.2%) | 0/38 (0%) | ||
| Infections and infestations | ||||
| Lip infection | 0/45 (0%) | 1/38 (2.6%) | ||
| Investigations | ||||
| Alkaline phosphatase increased | 1/45 (2.2%) | 0/38 (0%) | ||
| Aspartate aminotransferase increased | 1/45 (2.2%) | 0/38 (0%) | ||
| Lymphocyte count decreased | 1/45 (2.2%) | 0/38 (0%) | ||
| Neutrophil count decreased | 16/45 (35.6%) | 4/38 (10.5%) | ||
| White blood cell decreased | 2/45 (4.4%) | 1/38 (2.6%) | ||
| Metabolism and nutrition disorders | ||||
| Dehydration | 1/45 (2.2%) | 0/38 (0%) | ||
| Nervous system disorders | ||||
| Peripheral motor neuropathy | 3/45 (6.7%) | 0/38 (0%) | ||
| Peripheral sensory neuropathy | 2/45 (4.4%) | 2/38 (5.3%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 2/45 (4.4%) | 0/38 (0%) | ||
| Vascular disorders | ||||
| Thromboembolic event | 0/45 (0%) | 1/38 (2.6%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Cohort 1: HR+/HER2- | Cohort 2: TNBC | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 45/45 (100%) | 37/38 (97.4%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 9/45 (20%) | 6/38 (15.8%) | ||
| Febrile neutropenia | 1/45 (2.2%) | 0/38 (0%) | ||
| Cardiac disorders | ||||
| Chest pain - cardiac | 1/45 (2.2%) | 1/38 (2.6%) | ||
| Palpitations | 0/45 (0%) | 1/38 (2.6%) | ||
| Sinus tachycardia | 1/45 (2.2%) | 0/38 (0%) | ||
| Ear and labyrinth disorders | ||||
| Ear and labyrinth disorders - Other | 1/45 (2.2%) | 0/38 (0%) | ||
| Ear pain | 2/45 (4.4%) | 0/38 (0%) | ||
| Vertigo | 2/45 (4.4%) | 0/38 (0%) | ||
| Eye disorders | ||||
| Blurred vision | 1/45 (2.2%) | 0/38 (0%) | ||
| Cataract | 1/45 (2.2%) | 0/38 (0%) | ||
| Conjunctivitis | 1/45 (2.2%) | 0/38 (0%) | ||
| Eye disorders - Other | 2/45 (4.4%) | 1/38 (2.6%) | ||
| Watering eyes | 3/45 (6.7%) | 1/38 (2.6%) | ||
| Gastrointestinal disorders | ||||
| Abdominal distension | 0/45 (0%) | 1/38 (2.6%) | ||
| Abdominal pain | 2/45 (4.4%) | 2/38 (5.3%) | ||
| Colonic perforation | 0/45 (0%) | 1/38 (2.6%) | ||
| Constipation | 9/45 (20%) | 12/38 (31.6%) | ||
| Diarrhea | 10/45 (22.2%) | 4/38 (10.5%) | ||
| Dry mouth | 10/45 (22.2%) | 3/38 (7.9%) | ||
| Duodenal ulcer | 1/45 (2.2%) | 0/38 (0%) | ||
| Dyspepsia | 3/45 (6.7%) | 3/38 (7.9%) | ||
| Dysphagia | 3/45 (6.7%) | 0/38 (0%) | ||
| Esophagitis | 1/45 (2.2%) | 0/38 (0%) | ||
| Gastroesophageal reflux disease | 4/45 (8.9%) | 3/38 (7.9%) | ||
| Gastrointestinal disorders - Other | 2/45 (4.4%) | 2/38 (5.3%) | ||
| Mucositis oral | 12/45 (26.7%) | 5/38 (13.2%) | ||
| Nausea | 17/45 (37.8%) | 17/38 (44.7%) | ||
| Oral pain | 3/45 (6.7%) | 1/38 (2.6%) | ||
| Rectal hemorrhage | 0/45 (0%) | 1/38 (2.6%) | ||
| Stomach pain | 1/45 (2.2%) | 0/38 (0%) | ||
| Toothache | 1/45 (2.2%) | 0/38 (0%) | ||
| Vomiting | 8/45 (17.8%) | 7/38 (18.4%) | ||
| General disorders | ||||
| Chills | 1/45 (2.2%) | 1/38 (2.6%) | ||
| Edema limbs | 3/45 (6.7%) | 3/38 (7.9%) | ||
| Fatigue | 29/45 (64.4%) | 25/38 (65.8%) | ||
| Fever | 4/45 (8.9%) | 2/38 (5.3%) | ||
| Flu like symptoms | 1/45 (2.2%) | 1/38 (2.6%) | ||
| Gait disturbance | 0/45 (0%) | 1/38 (2.6%) | ||
| General disorders and administration site conditions - Other | 0/45 (0%) | 0/38 (0%) | ||
| Infusion site extravasation | 0/45 (0%) | 1/38 (2.6%) | ||
| Non-cardiac chest pain | 2/45 (4.4%) | 1/38 (2.6%) | ||
| Pain | 12/45 (26.7%) | 6/38 (15.8%) | ||
| Hepatobiliary disorders | ||||
| Hepatobiliary disorders - Other | 1/45 (2.2%) | 0/38 (0%) | ||
| Infections and infestations | ||||
| Breast infection | 1/45 (2.2%) | 0/38 (0%) | ||
| Gum infection | 1/45 (2.2%) | 0/38 (0%) | ||
| Infections and infestations - Other | 1/45 (2.2%) | 1/38 (2.6%) | ||
| Lung infection | 0/45 (0%) | 1/38 (2.6%) | ||
| Sinusitis | 1/45 (2.2%) | 0/38 (0%) | ||
| Skin infection | 1/45 (2.2%) | 0/38 (0%) | ||
| Tooth infection | 2/45 (4.4%) | 0/38 (0%) | ||
| Upper respiratory infection | 1/45 (2.2%) | 3/38 (7.9%) | ||
| Urinary tract infection | 7/45 (15.6%) | 3/38 (7.9%) | ||
| Vaginal infection | 0/45 (0%) | 1/38 (2.6%) | ||
| Injury, poisoning and procedural complications | ||||
| Venous injury | 1/45 (2.2%) | 0/38 (0%) | ||
| Investigations | ||||
| Alanine aminotransferase increased | 8/45 (17.8%) | 4/38 (10.5%) | ||
| Alkaline phosphatase increased | 4/45 (8.9%) | 3/38 (7.9%) | ||
| Aspartate aminotransferase increased | 9/45 (20%) | 3/38 (7.9%) | ||
| Blood bilirubin increased | 0/45 (0%) | 1/38 (2.6%) | ||
| CD4 lymphocytes decreased | 1/45 (2.2%) | 0/38 (0%) | ||
| Investigations - Other | 2/45 (4.4%) | 1/38 (2.6%) | ||
| Lymphocyte count decreased | 1/45 (2.2%) | 0/38 (0%) | ||
| Neutrophil count decreased | 2/45 (4.4%) | 5/38 (13.2%) | ||
| Platelet count decreased | 3/45 (6.7%) | 3/38 (7.9%) | ||
| Weight loss | 3/45 (6.7%) | 2/38 (5.3%) | ||
| White blood cell decreased | 4/45 (8.9%) | 2/38 (5.3%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 11/45 (24.4%) | 6/38 (15.8%) | ||
| Dehydration | 1/45 (2.2%) | 1/38 (2.6%) | ||
| Hypercalcemia | 0/45 (0%) | 1/38 (2.6%) | ||
| Hyperglycemia | 5/45 (11.1%) | 1/38 (2.6%) | ||
| Hyperkalemia | 1/45 (2.2%) | 0/38 (0%) | ||
| Hypoalbuminemia | 3/45 (6.7%) | 1/38 (2.6%) | ||
| Hypocalcemia | 2/45 (4.4%) | 0/38 (0%) | ||
| Hypoglycemia | 1/45 (2.2%) | 0/38 (0%) | ||
| Hypokalemia | 2/45 (4.4%) | 4/38 (10.5%) | ||
| Hypomagnesemia | 3/45 (6.7%) | 1/38 (2.6%) | ||
| Hyponatremia | 2/45 (4.4%) | 0/38 (0%) | ||
| Metabolism and nutrition disorders - Other | 0/45 (0%) | 1/38 (2.6%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 8/45 (17.8%) | 4/38 (10.5%) | ||
| Back pain | 1/45 (2.2%) | 5/38 (13.2%) | ||
| Bone pain | 5/45 (11.1%) | 3/38 (7.9%) | ||
| Buttock pain | 1/45 (2.2%) | 0/38 (0%) | ||
| Chest wall pain | 2/45 (4.4%) | 2/38 (5.3%) | ||
| Flank pain | 1/45 (2.2%) | 0/38 (0%) | ||
| Generalized muscle weakness | 0/45 (0%) | 3/38 (7.9%) | ||
| Joint effusion | 0/45 (0%) | 1/38 (2.6%) | ||
| Muscle weakness lower limb | 2/45 (4.4%) | 0/38 (0%) | ||
| Muscle weakness right-sided | 1/45 (2.2%) | 0/38 (0%) | ||
| Muscle weakness upper limb | 0/45 (0%) | 1/38 (2.6%) | ||
| Musculoskeletal and connective tissue disorder - Other | 3/45 (6.7%) | 1/38 (2.6%) | ||
| Myalgia | 8/45 (17.8%) | 5/38 (13.2%) | ||
| Neck pain | 1/45 (2.2%) | 2/38 (5.3%) | ||
| Pain in extremity | 5/45 (11.1%) | 2/38 (5.3%) | ||
| Nervous system disorders | ||||
| Concentration impairment | 8/45 (17.8%) | 0/38 (0%) | ||
| Dizziness | 3/45 (6.7%) | 3/38 (7.9%) | ||
| Dysgeusia | 6/45 (13.3%) | 2/38 (5.3%) | ||
| Facial nerve disorder | 0/45 (0%) | 1/38 (2.6%) | ||
| Headache | 7/45 (15.6%) | 3/38 (7.9%) | ||
| Memory impairment | 0/45 (0%) | 1/38 (2.6%) | ||
| Movements involuntary | 0/45 (0%) | 1/38 (2.6%) | ||
| Nervous system disorders - Other | 2/45 (4.4%) | 0/38 (0%) | ||
| Paresthesia | 1/45 (2.2%) | 2/38 (5.3%) | ||
| Peripheral motor neuropathy | 12/45 (26.7%) | 5/38 (13.2%) | ||
| Peripheral sensory neuropathy | 17/45 (37.8%) | 9/38 (23.7%) | ||
| Psychiatric disorders | ||||
| Anxiety | 6/45 (13.3%) | 4/38 (10.5%) | ||
| Depression | 3/45 (6.7%) | 3/38 (7.9%) | ||
| Insomnia | 2/45 (4.4%) | 4/38 (10.5%) | ||
| Renal and urinary disorders | ||||
| Hematuria | 0/45 (0%) | 1/38 (2.6%) | ||
| Urinary urgency | 1/45 (2.2%) | 0/38 (0%) | ||
| Reproductive system and breast disorders | ||||
| Breast pain | 2/45 (4.4%) | 2/38 (5.3%) | ||
| Vaginal hemorrhage | 1/45 (2.2%) | 0/38 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 11/45 (24.4%) | 2/38 (5.3%) | ||
| Dyspnea | 14/45 (31.1%) | 5/38 (13.2%) | ||
| Epistaxis | 1/45 (2.2%) | 0/38 (0%) | ||
| Hoarseness | 2/45 (4.4%) | 0/38 (0%) | ||
| Pleural effusion | 2/45 (4.4%) | 1/38 (2.6%) | ||
| Pleuritic pain | 0/45 (0%) | 1/38 (2.6%) | ||
| Pneumonitis | 2/45 (4.4%) | 0/38 (0%) | ||
| Postnasal drip | 0/45 (0%) | 1/38 (2.6%) | ||
| Respiratory, thoracic and mediastinal disorders - Other | 3/45 (6.7%) | 0/38 (0%) | ||
| Sinus disorder | 1/45 (2.2%) | 0/38 (0%) | ||
| Sore throat | 0/45 (0%) | 3/38 (7.9%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 26/45 (57.8%) | 15/38 (39.5%) | ||
| Dry skin | 4/45 (8.9%) | 1/38 (2.6%) | ||
| Pruritus | 1/45 (2.2%) | 0/38 (0%) | ||
| Rash maculo-papular | 5/45 (11.1%) | 1/38 (2.6%) | ||
| Rash maculo-papular | 0/45 (0%) | 0/38 (0%) | ||
| Skin and subcutaneous tissue disorders - Other | 2/45 (4.4%) | 0/38 (0%) | ||
| Skin hyperpigmentation | 0/45 (0%) | 1/38 (2.6%) | ||
| Urticaria | 0/45 (0%) | 1/38 (2.6%) | ||
| Vascular disorders | ||||
| Hot flashes | 1/45 (2.2%) | 3/38 (7.9%) | ||
| Hypertension | 1/45 (2.2%) | 3/38 (7.9%) | ||
| Lymphedema | 0/45 (0%) | 1/38 (2.6%) | ||
| Thromboembolic event | 1/45 (2.2%) | 0/38 (0%) | ||
| Vascular disorders - Other | 0/45 (0%) | 1/38 (2.6%) | ||
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE 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 | Dr. Erica Mayer |
|---|---|
| Organization | Dana-Farber Cancer Institute |
| Phone | 617-632-2335 |
| Erica_Mayer@dfci.harvard.edu |
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