NeoPHOEBE: Neoadjuvant Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive Primary Breast Cancer
Study Details
Study Description
Brief Summary
This randomized, parallel cohort, two stage, double-blind, placebo-controlled study evaluated the oral PI3K inhibitor BKM120 in combination with trastuzumab and paclitaxel in HER2-positive, PIK3CA wild-type and PIK3CA mutant primary breast cancer prior to surgery (neo-adjuvant setting).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
NeoPHOEBE evaluated the efficacy (as defined by pCR) of BKM120 (an oral PI3K inhibitor) in combination with trastuzumab and paclitaxel in a randomized, placebo-controlled, neo-adjuvant study in women diagnosed with primary breast cancer >1.5 cm (by US or MRI) with centrally confirmed HER2 overexpression or amplification, who have not previously undergone treatment for invasive breast cancer.
Prior to the initiation of paclitaxel, there was a 6-week "biologic window" with trastuzumab plus BKM120 or placebo only. The study was conducted separately in two cohorts (PIK3CA mutated and PI3K3CA wild-type) using a two-stage approach. Within each cohort patients were randomized into one of the following treatment arms:
Arm 1: BKM120 plus trastuzumab for 6 weeks followed by BKM120 and trastuzumab plus weekly paclitaxel for an additional 12 weeks.
Arm 2: BKM120 placebo plus trastuzumab for 6 weeks followed by BKM120 placebo plus trastuzumab plus weekly paclitaxel for an additional 12 weeks.
After completion of study treatment, patients were to have undergone definitive surgery.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: BKM120 + Trastuzumab + paclitaxel BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. |
Drug: BKM120
Neo-adjuvant BKM120 (oral pan-class I PI3K inhibitor, continuous daily dosing). BKM120 was administered orally 100 mg/day.
Other Names:
Drug: Trastuzumab
Trastuzumab is a humanized monoclonal antibody directed against the extracellular juxtamembrane domain of the HER2 receptor. Administered 4mg/kg i.v. load followed by 2mg/kg i.v. weekly.
Drug: Paclitaxel
Paclitaxel is a cytotoxic agent with proven antitumor activity in a variety of solid tumors. The antitumor activity of paclitaxel is based on tubulin-binding and stabilization of non-functional microtubule bundles, thereby blocking normal mitotic spindle development and subsequent cell division. Administered weekly 80mg/m2 i.v.
|
Placebo Comparator: BKM120 PBO + Trastuzumab + paclitaxel BKM120 placebo in combination with trastuzumab and paclitaxel |
Drug: Trastuzumab
Trastuzumab is a humanized monoclonal antibody directed against the extracellular juxtamembrane domain of the HER2 receptor. Administered 4mg/kg i.v. load followed by 2mg/kg i.v. weekly.
Drug: Paclitaxel
Paclitaxel is a cytotoxic agent with proven antitumor activity in a variety of solid tumors. The antitumor activity of paclitaxel is based on tubulin-binding and stabilization of non-functional microtubule bundles, thereby blocking normal mitotic spindle development and subsequent cell division. Administered weekly 80mg/m2 i.v.
Drug: BKM120 Placebo
Neoadjuvant BKM120 placebo Administered orally 100 mg/day.
|
Outcome Measures
Primary Outcome Measures
- Pathological Complete Response (pCR) Rate at the Time of Surgery - All Participants [After 6 weeks]
Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.
- Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Wild Type (WT) [After 6 weeks]
Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.
- Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Mutant (MT) [After 6 weeks]
Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.
Secondary Outcome Measures
- Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - All Participants [After week 6]
Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria.
- Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Wild Type Participants [After week 6]
Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria.
- Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Mutant Participants [After week 6]
Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria.
- Rate of Breast Conserving Surgery (Most Radical Surgery) [18 weeks]
Rate of patients with breast conserving surgery. Participants who did not have breast surgery were also considered as having breast conservation surgery (BCS)
- Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per GBG Definition [After Week 6]
Rate of pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 [GBG definition]). If patient had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such patient was considered to be pN0 for both secondary pCR definitions. Surgical breast and axillary node resection specimens were evaluated for pathologic tumor response according to NSABP guidelines.
- Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per MD Anderson Definition [After Week 6]
Rate of pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition]). If a patient had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such patient was considered to be pN0 for both secondary pCR definitions.
- Overall Objective Response Rate (ORR) Prior to Surgery for All Participants [prior to surgery]
Number of Overall objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered.
- Percentage of Participants With pCR Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+) [After Week 6]
pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 [GBG definition]); pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition]). If participant had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such participant was considered to be pN0 for both secondary pCR definitions.
- Percentage of Participants With pCR Rates by Hormone Receptor Status Negative Estrogen Receptor (ER-) [After Week 6]
pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 [GBG definition]); pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition]). If participant had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such participant was considered to be pN0 for both secondary pCR definitions.
- Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+) [After Week 6]
Objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered.
- Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Negative Estrogen Receptor (ER-) [After Week 6]
Objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered.
- Percentage of Participants With Remaining Ductal Carcinoma in Situ (DCIS) (ypTis) [18 weeks]
This included participants at definitive surgery irrespective of lymph node status
- Percentage of Participants With Node-negative Disease at Definitive Surgery (ypN0) [18 weeks]
Node-negative disease at definitive surgery (ypN0) were considered as binary variables of 'response' versus 'non response'.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Patient had provided a signed study ICF prior to any screening procedure
-
Patient was a female ≥ 18 years of age
-
Patient has an ECOG performance status of 0-1
-
Patient has a unilateral (multifocal or multicentric disease allowed), histologically confirmed, newly diagnosed early breast cancer >2cm by clinical examination and/or
1.5 cm confirmed by ultrasound or by MRI
-
Patient has tumor tissue available for central review of ER, HER2 and PI3K status with centrally confirmed HER2-positive disease and known PI3KCA mutation status
-
Patient has adequate bone marrow, renal and liver function
-
Patient is able to swallow and retain oral medication
Exclusion Criteria:
-
Patient has received prior systemic treatment for currently diagnosed disease
-
Patient has a known contraindications, hypersensitivity or intolerance to trastuzumab, paclitaxel or products containing cremophor
-
Patient has bilateral breast cancer or metastatic disease or inflammatory breast cancer
-
LVEF below 50% as determined by MUGA scan or ECHO
-
Patient has active cardiac disease or a history of cardiac abnormalities as defined in the protocol
-
Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120
-
Patient is currently receiving warfarin or other coumarin derived anti-coagulants
-
Patient is currently receiving chronic treatment with corticosteroids or another immunosuppressive agents (standard premedication for paclitaxel and local applications allowed)
-
Patient is currently receiving treatment with drugs known to be strong inhibitors or inducers of CYP3A
-
Patient has certain scores on an anxiety and depression mood questionnaires
-
Pregnant or nursing (lactating) women or patients not willing to apply apply highly effective contraception as defined in the protocol
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Novartis Investigative Site | Parkville | Victoria | Australia | 3002 |
2 | Novartis Investigative Site | Parkville | Victoria | Australia | 3050 |
3 | Novartis Investigative Site | Salzburg | Austria | 5020 | |
4 | Novartis Investigative Site | Lubeck | Germany | 23538 | |
5 | Novartis Investigative Site | Offenbach | Germany | 63069 | |
6 | Novartis Investigative Site | Sevilla | Andalucia | Spain | 41013 |
7 | Novartis Investigative Site | Madrid | Spain | 28222 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
- Breast International Group
- German Breast Group
- SOLTI Breast Cancer Research Group
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CBKM120F2203
Study Results
Participant Flow
Recruitment Details | Planned: Minimum 128 patients (in case of early stopping of both cohorts), maximum: 220 patients (if both cohorts would have proceeded into stage 2), and 174 patients if one cohort would have stopped early. |
---|---|
Pre-assignment Detail | Screened: 68 patients Randomized and analyzed (safety and efficacy): 50 patients |
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel | Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. | BKM120 placebo in combination with trastuzumab and paclitaxel |
Period Title: Overall Study | ||
STARTED | 25 | 25 |
Randomized to the wt Cohort | 21 | 21 |
Randomized to the mt Cohort | 4 | 4 |
COMPLETED | 14 | 23 |
NOT COMPLETED | 11 | 2 |
Baseline Characteristics
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel | Trastuzumab + BKM120 PBO + Paclitaxel | Total |
---|---|---|---|
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. | BKM120 placebo in combination with trastuzumab and paclitaxel | Total of all reporting groups |
Overall Participants | 25 | 25 | 50 |
Age (Years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [Years] |
51.1
(11.5)
|
51.3
(11.2)
|
51.2
(11.2)
|
Sex: Female, Male (Count of Participants) | |||
Female |
25
100%
|
25
100%
|
50
100%
|
Male |
0
0%
|
0
0%
|
0
0%
|
Race/Ethnicity, Customized (participants) [Number] | |||
Caucasian/white |
21
84%
|
24
96%
|
45
90%
|
Asian/Oriental |
3
12%
|
1
4%
|
4
8%
|
Other |
1
4%
|
0
0%
|
1
2%
|
Outcome Measures
Title | Pathological Complete Response (pCR) Rate at the Time of Surgery - All Participants |
---|---|
Description | Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR. |
Time Frame | After 6 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment. |
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel | Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. | BKM120 placebo in combination with trastuzumab and paclitaxel |
Measure Participants | 25 | 25 |
Number (95% Confidence Interval) [Percentage of participants] |
32.0
128%
|
40.0
160%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Comments | All participantss | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.811 |
Comments | ||
Method | Fisher Exact | |
Comments | (one-sided) |
Title | Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Wild Type (WT) |
---|---|
Description | Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR. |
Time Frame | After 6 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment. |
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel | Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. | BKM120 placebo in combination with trastuzumab and paclitaxel |
Measure Participants | 21 | 21 |
Number (95% Confidence Interval) [Percentage of participants] |
33.3
133.2%
|
42.9
171.6%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Comments | wild type cohort | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.830 |
Comments | ||
Method | Fisher Exact | |
Comments | (one-sided) |
Title | Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Mutant (MT) |
---|---|
Description | Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR. |
Time Frame | After 6 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment. |
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel | Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. | BKM120 placebo in combination with trastuzumab and paclitaxel |
Measure Participants | 4 | 4 |
Number (95% Confidence Interval) [Percentage of participants] |
25.0
100%
|
25.0
100%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Comments | mutant cohort | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.786 |
Comments | ||
Method | Fisher Exact | |
Comments | (one-sided) |
Title | Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - All Participants |
---|---|
Description | Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. |
Time Frame | After week 6 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment. |
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel | Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. | BKM120 placebo in combination with trastuzumab and paclitaxel |
Measure Participants | 25 | 25 |
Number (95% Confidence Interval) [Percentage of participants] |
56.0
224%
|
44.0
176%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Comments | All participants | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.286 |
Comments | ||
Method | Fisher Exact | |
Comments | (one-sided) |
Title | Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Wild Type Participants |
---|---|
Description | Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. |
Time Frame | After week 6 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment. |
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel | Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. | BKM120 placebo in combination with trastuzumab and paclitaxel |
Measure Participants | 21 | 21 |
Number (95% Confidence Interval) [Percentage of participants] |
61.9
247.6%
|
42.9
171.6%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Comments | wild type cohort | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.177 |
Comments | ||
Method | Fisher Exact | |
Comments | (one-sided) |
Title | Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Mutant Participants |
---|---|
Description | Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. |
Time Frame | After week 6 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment. |
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel | Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. | BKM120 placebo in combination with trastuzumab and paclitaxel |
Measure Participants | 4 | 4 |
Number (95% Confidence Interval) [Percentage of participants] |
25.0
100%
|
50.0
200%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Comments | mutant cohort | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.929 |
Comments | ||
Method | Fisher Exact | |
Comments | (one-sided) |
Title | Rate of Breast Conserving Surgery (Most Radical Surgery) |
---|---|
Description | Rate of patients with breast conserving surgery. Participants who did not have breast surgery were also considered as having breast conservation surgery (BCS) |
Time Frame | 18 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment. |
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel | Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. | BKM120 placebo in combination with trastuzumab and paclitaxel |
Measure Participants | 25 | 25 |
Number (95% Confidence Interval) [Percentage of participants] |
60.0
240%
|
68.0
272%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.811 |
Comments | ||
Method | Fisher Exact | |
Comments | (one-sided) |
Title | Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per GBG Definition |
---|---|
Description | Rate of pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 [GBG definition]). If patient had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such patient was considered to be pN0 for both secondary pCR definitions. Surgical breast and axillary node resection specimens were evaluated for pathologic tumor response according to NSABP guidelines. |
Time Frame | After Week 6 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment. |
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel | Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. | BKM120 placebo in combination with trastuzumab and paclitaxel |
Measure Participants | 25 | 25 |
Number (95% Confidence Interval) [Percentage of participants] |
20.0
80%
|
28.0
112%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.840 |
Comments | ||
Method | Fisher Exact | |
Comments | (one-sided) |
Title | Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per MD Anderson Definition |
---|---|
Description | Rate of pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition]). If a patient had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such patient was considered to be pN0 for both secondary pCR definitions. |
Time Frame | After Week 6 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment. |
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel | Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. | BKM120 placebo in combination with trastuzumab and paclitaxel |
Measure Participants | 25 | 25 |
Number (95% Confidence Interval) [Percentage of participants] |
32.0
128%
|
36.0
144%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.724 |
Comments | ||
Method | Fisher Exact | |
Comments | (one-sided) |
Title | Overall Objective Response Rate (ORR) Prior to Surgery for All Participants |
---|---|
Description | Number of Overall objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered. |
Time Frame | prior to surgery |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment. |
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel | Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. | BKM120 placebo in combination with trastuzumab and paclitaxel |
Measure Participants | 25 | 25 |
Number (95% Confidence Interval) [Percentage of participants] |
56.0
224%
|
76.0
304%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Comments | All participants | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.964 |
Comments | ||
Method | Fisher Exact | |
Comments | (one-sided) |
Title | Percentage of Participants With pCR Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+) |
---|---|
Description | pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 [GBG definition]); pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition]). If participant had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such participant was considered to be pN0 for both secondary pCR definitions. |
Time Frame | After Week 6 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment. |
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel ( ER+) | Trastuzumab + BKM120 PBO + Paclitaxel (ER+) |
---|---|---|
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel in positive estrogen receptor participants. | BKM120 placebo in combination with trastuzumab and paclitaxel in patients with positive estrogen receptor participants |
Measure Participants | 16 | 15 |
Number (95% Confidence Interval) [Percentage of participants] |
31.3
125.2%
|
26.7
106.8%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Comments | For ER+ participants - pCR | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.546 |
Comments | ||
Method | Fisher Exact | |
Comments | (one-sided) |
Title | Percentage of Participants With pCR Rates by Hormone Receptor Status Negative Estrogen Receptor (ER-) |
---|---|
Description | pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 [GBG definition]); pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition]). If participant had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such participant was considered to be pN0 for both secondary pCR definitions. |
Time Frame | After Week 6 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment. |
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel (ER-) | Trastuzumab + BKM120 PBO + Paclitaxel (ER-) |
---|---|---|
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel in negative estrogen receptor participants. | BKM120 placebo in combination with trastuzumab and paclitaxel in negative estrogen receptor participants |
Measure Participants | 9 | 10 |
Number (95% Confidence Interval) [Percentage of participants] |
33.3
133.2%
|
60.0
240%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Comments | For ER- participants - pCR | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.949 |
Comments | ||
Method | Fisher Exact | |
Comments | (one-sided) |
Title | Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+) |
---|---|
Description | Objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered. |
Time Frame | After Week 6 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment. |
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel (ER+) | Trastuzumab + BKM120 PBO + Paclitaxel (ER+) |
---|---|---|
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel in positive estrogen receptor participants. | BKM120 placebo in combination with trastuzumab and paclitaxel in positive estrogen receptor participants |
Measure Participants | 16 | 15 |
Number (95% Confidence Interval) [Percentage of participants] |
68.8
275.2%
|
33.3
133.2%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Comments | For ER+ participants - ORR | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.053 |
Comments | ||
Method | Fisher Exact | |
Comments | (one-sided) |
Title | Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Negative Estrogen Receptor (ER-) |
---|---|
Description | Objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered. |
Time Frame | After Week 6 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment. |
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel (ER-) | Trastuzumab + BKM120 PBO + Paclitaxel (ER-) |
---|---|---|
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel in negative estrogen receptor participants. | BKM120 placebo in combination with trastuzumab and paclitaxel in negative estrogen receptor participants |
Measure Participants | 9 | 10 |
Number (95% Confidence Interval) [Percentage of participants] |
33.3
133.2%
|
60.0
240%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Comments | For ER- participants - ORR | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.949 |
Comments | ||
Method | Fisher Exact | |
Comments | (one-sided) |
Title | Percentage of Participants With Remaining Ductal Carcinoma in Situ (DCIS) (ypTis) |
---|---|
Description | This included participants at definitive surgery irrespective of lymph node status |
Time Frame | 18 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment. |
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel | Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. | BKM120 placebo in combination with trastuzumab and paclitaxel |
Measure Participants | 25 | 25 |
Number (95% Confidence Interval) [Percentage of participants] |
12.0
48%
|
12.0
48%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.666 |
Comments | ||
Method | Fisher Exact | |
Comments | (one-sided) |
Title | Percentage of Participants With Node-negative Disease at Definitive Surgery (ypN0) |
---|---|
Description | Node-negative disease at definitive surgery (ypN0) were considered as binary variables of 'response' versus 'non response'. |
Time Frame | 18 weeks |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment. |
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel | Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. | BKM120 placebo in combination with trastuzumab and paclitaxel |
Measure Participants | 25 | 25 |
Number (95% Confidence Interval) [Percentage of participants] |
52.0
208%
|
60.0
240%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Trastuzumab + BKM120 + Paclitaxel, Trastuzumab + BKM120 PBO + Paclitaxel |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.803 |
Comments | ||
Method | Fisher Exact | |
Comments | (one-sided) |
Adverse Events
Time Frame | AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. | |||
---|---|---|---|---|
Adverse Event Reporting Description | All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months. | |||
Arm/Group Title | Trastuzumab + BKM120 + Paclitaxel | Trastuzumab + BKM120 PBO + Paclitaxel | ||
Arm/Group Description | BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. | BKM120 placebo in combination with trastuzumab and paclitaxel | ||
All Cause Mortality |
||||
Trastuzumab + BKM120 + Paclitaxel | Trastuzumab + BKM120 PBO + Paclitaxel | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/25 (0%) | 0/25 (0%) | ||
Serious Adverse Events |
||||
Trastuzumab + BKM120 + Paclitaxel | Trastuzumab + BKM120 PBO + Paclitaxel | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 8/25 (32%) | 2/25 (8%) | ||
Gastrointestinal disorders | ||||
Diarrhoea | 1/25 (4%) | 0/25 (0%) | ||
General disorders | ||||
Catheter site pain | 1/25 (4%) | 0/25 (0%) | ||
Pyrexia | 1/25 (4%) | 0/25 (0%) | ||
Thrombosis in device | 0/25 (0%) | 1/25 (4%) | ||
Hepatobiliary disorders | ||||
Hepatotoxicity | 1/25 (4%) | 0/25 (0%) | ||
Immune system disorders | ||||
Hypersensitivity | 1/25 (4%) | 0/25 (0%) | ||
Infections and infestations | ||||
Acute sinusitis | 0/25 (0%) | 1/25 (4%) | ||
Pneumonia | 1/25 (4%) | 0/25 (0%) | ||
Investigations | ||||
Hepatic enzyme increased | 2/25 (8%) | 0/25 (0%) | ||
Nervous system disorders | ||||
Headache | 0/25 (0%) | 1/25 (4%) | ||
Psychiatric disorders | ||||
Mental disorder | 1/25 (4%) | 0/25 (0%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Pulmonary oedema | 1/25 (4%) | 0/25 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Trastuzumab + BKM120 + Paclitaxel | Trastuzumab + BKM120 PBO + Paclitaxel | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 21/25 (84%) | 19/25 (76%) | ||
Blood and lymphatic system disorders | ||||
Anemia | 17/25 (68%) | 18/25 (72%) | ||
Leukopenia | 11/25 (44%) | 15/25 (60%) | ||
Lymphopenia | 11/25 (44%) | 8/25 (32%) | ||
Neutropenia | 6/25 (24%) | 9/25 (36%) | ||
Thrombopenia | 4/25 (16%) | 0/25 (0%) | ||
Cardiac disorders | ||||
Cardiac disorders not yet listed | 1/25 (4%) | 3/25 (12%) | ||
Ear and labyrinth disorders | ||||
Ear and labyrinth disorders | 1/25 (4%) | 2/25 (8%) | ||
Eye disorders | ||||
Eye disorders | 5/25 (20%) | 3/25 (12%) | ||
Gastrointestinal disorders | ||||
Abdominal pain | 2/25 (8%) | 4/25 (16%) | ||
Constipation | 4/25 (16%) | 7/25 (28%) | ||
Diarrhea | 15/25 (60%) | 10/25 (40%) | ||
Dysgeusia | 4/25 (16%) | 5/25 (20%) | ||
Dyspepsia | 4/25 (16%) | 4/25 (16%) | ||
Mucositis | 19/25 (76%) | 12/25 (48%) | ||
Nausea | 11/25 (44%) | 8/25 (32%) | ||
Other gastrointestinal disorders | 7/25 (28%) | 7/25 (28%) | ||
Upper abdominal pain | 5/25 (20%) | 1/25 (4%) | ||
Vomiting | 3/25 (12%) | 2/25 (8%) | ||
General disorders | ||||
Chills | 1/25 (4%) | 4/25 (16%) | ||
Fatigue | 13/25 (52%) | 14/25 (56%) | ||
Oedema | 3/25 (12%) | 8/25 (32%) | ||
Other general disorders and administration site conditions | 2/25 (8%) | 1/25 (4%) | ||
Immune system disorders | ||||
Allergic reactions | 3/25 (12%) | 1/25 (4%) | ||
Infections and infestations | ||||
Fever without neutropenia | 7/25 (28%) | 3/25 (12%) | ||
Infection | 12/25 (48%) | 19/25 (76%) | ||
Injury, poisoning and procedural complications | ||||
Injury and poisoning and procedural complications | 1/25 (4%) | 2/25 (8%) | ||
Investigations | ||||
Decreased calcium | 9/25 (36%) | 11/25 (44%) | ||
Decreased potassium | 6/25 (24%) | 2/25 (8%) | ||
Decreased serum albumin | 5/25 (20%) | 2/25 (8%) | ||
Decreased sodium | 9/25 (36%) | 7/25 (28%) | ||
Increased ALT | 21/25 (84%) | 18/25 (72%) | ||
Increased AP | 6/25 (24%) | 6/25 (24%) | ||
Increased AST | 19/25 (76%) | 9/25 (36%) | ||
Increased FPG | 13/25 (52%) | 8/25 (32%) | ||
Increased GGT | 8/25 (32%) | 7/25 (28%) | ||
Increased aPTT | 5/25 (20%) | 6/25 (24%) | ||
Increased potassium | 3/25 (12%) | 11/25 (44%) | ||
Increased serum creatinine | 1/25 (4%) | 2/25 (8%) | ||
Increased sodium | 4/25 (16%) | 2/25 (8%) | ||
Increased total bilirubin | 2/25 (8%) | 0/25 (0%) | ||
Increased total cholesterol | 14/25 (56%) | 14/25 (56%) | ||
Increased triglycerides | 5/25 (20%) | 6/25 (24%) | ||
Increased uric acid | 6/25 (24%) | 10/25 (40%) | ||
Metabolism and nutrition disorders | ||||
Anorexia | 5/25 (20%) | 1/25 (4%) | ||
Musculoskeletal and connective tissue disorders | ||||
Arthralgia | 7/25 (28%) | 10/25 (40%) | ||
Bone pain | 3/25 (12%) | 5/25 (20%) | ||
Myalgia | 3/25 (12%) | 5/25 (20%) | ||
Other musculo-skeletal and connective tissue disorders | 2/25 (8%) | 1/25 (4%) | ||
Nervous system disorders | ||||
Dizziness | 9/25 (36%) | 4/25 (16%) | ||
Headache | 2/25 (8%) | 8/25 (32%) | ||
Other neurological disorder | 3/25 (12%) | 2/25 (8%) | ||
Peripheral sensory neuropathy | 14/25 (56%) | 16/25 (64%) | ||
Psychiatric disorders | ||||
Anxiety | 5/25 (20%) | 3/25 (12%) | ||
Depression | 6/25 (24%) | 8/25 (32%) | ||
Insomnia | 3/25 (12%) | 4/25 (16%) | ||
Psychiatric disorders | 2/25 (8%) | 0/25 (0%) | ||
Renal and urinary disorders | ||||
Renal and urinary disorders | 2/25 (8%) | 0/25 (0%) | ||
Reproductive system and breast disorders | ||||
Reproductive system and breast disorders | 1/25 (4%) | 3/25 (12%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Dyspnea | 2/25 (8%) | 6/25 (24%) | ||
Epistaxis | 0/25 (0%) | 5/25 (20%) | ||
Other respiratory and mediastinal disorders | 5/25 (20%) | 6/25 (24%) | ||
Skin and subcutaneous tissue disorders | ||||
Alopecia | 18/25 (72%) | 17/25 (68%) | ||
Dry skin | 5/25 (20%) | 4/25 (16%) | ||
Erythema | 3/25 (12%) | 5/25 (20%) | ||
Nail disorder | 5/25 (20%) | 5/25 (20%) | ||
Other skin and subcutaneous tissue disorders | 5/25 (20%) | 7/25 (28%) | ||
Pruritus | 10/25 (40%) | 5/25 (20%) | ||
Rash maculo-papular | 15/25 (60%) | 12/25 (48%) | ||
Rash other than macular-papular or NOS | 8/25 (32%) | 8/25 (32%) | ||
Vascular disorders | ||||
Hot flushes | 5/25 (20%) | 7/25 (28%) | ||
Vascular disorders | 1/25 (4%) | 3/25 (12%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
Name/Title | Study Director |
---|---|
Organization | Novartis Pharmaceuticals |
Phone | 862-778-8300 |
trialandresults.registries@novartis.com |
- CBKM120F2203