Trial Outcomes & Findings for Paclitaxel + Trastuzumab + Pertuzumab as Pre-Op for Inflammatory BrCa (NCT NCT01796197)

NCT ID: NCT01796197

Last Updated: 2026-02-05

Results Overview

Pathologic complete response (pCR) is defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative treatment. Participants whose disease is not surgically resectable following preoperative treatment are considered as not having pCR.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 23 participants
• Primary outcome timeframe: 18 weeks
• Results posted on: 2026-02-05

Participant Flow

August 2013 to June 2018

Participants are not being evaluated based on their post-operative treatment option. Two options are provided to the participants in order to best treat them based on the nature of their disease.

Participant milestones

Measure	Treatment Arm Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care.
Overall Study STARTED	23
Overall Study COMPLETED	21
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Measure	Treatment Arm Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care.
Overall Study Lost to Follow-up	1
Overall Study Lack of Efficacy	1

Baseline Characteristics

Paclitaxel + Trastuzumab + Pertuzumab as Pre-Op for Inflammatory BrCa

Baseline characteristics by cohort

Measure	Treatment Arm n=23 Participants Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care.
Age, Continuous	48 years n=25 Participants
Sex: Female, Male Female	23 Participants n=25 Participants
Sex: Female, Male Male	0 Participants n=25 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=25 Participants
Race (NIH/OMB) Asian	1 Participants n=25 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=25 Participants
Race (NIH/OMB) Black or African American	1 Participants n=25 Participants
Race (NIH/OMB) White	19 Participants n=25 Participants
Race (NIH/OMB) More than one race	1 Participants n=25 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=25 Participants
Region of Enrollment United States	23 participants n=25 Participants
Estrogen Receptor Status Negative	11 Participants n=25 Participants
Estrogen Receptor Status Positive	12 Participants n=25 Participants
Breast Cancer Stage IIIB	16 Participants n=25 Participants
Breast Cancer Stage IIIC	6 Participants n=25 Participants
Breast Cancer Stage IV	1 Participants n=25 Participants

PRIMARY outcome

Timeframe: 18 weeks

Population: Subjects evaluable for response. Participants are not being evaluated based on their post-operative treatment option. Two options are provided to the participants in order to best treat them based on the nature of their disease

Pathologic complete response (pCR) is defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative treatment. Participants whose disease is not surgically resectable following preoperative treatment are considered as not having pCR.

Outcome measures

Measure

Treatment Arm n=21 Participants Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care.

Percentages of Participants With Pathologic Complete Response

48 percentage of participants Interval 29.0 to 67.0

PRIMARY outcome

Timeframe: 18 Weeks

Population: Subjects evaluable for response. Participants are not being evaluated based on their post-operative treatment option. Two options are provided to the participants in order to best treat them based on the nature of their disease

Residual cancer burden is calculated an then categorized based on the methods described in the following: Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol 2007;25(28): 4414-22.

This method uses tumor size, the proportion of that tumor that is invasive carcinoma, the number of axillary lymph nodes containing metastatic carcinoma and the diameter of the largest metastasis in an axillary lymph node. These parameters are combined in a formula that outputs a RCB index. This index is divided into 4 categories: RCB-0, RCB-I, RCB-II, and RCB-III. The previous categories are in order of increasing severity of RCB.

Outcome measures

Measure	Treatment Arm n=21 Participants Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care.
Residual Cancer Burden Rate RCB-0	48 percentage of participants Interval 29.0 to 67.0
Residual Cancer Burden Rate RCB-I	33 percentage of participants Interval 17.0 to 54.0
Residual Cancer Burden Rate RCB-II	5 percentage of participants Interval 2.0 to 21.0
Residual Cancer Burden Rate RCB-III	14 percentage of participants Interval 4.0 to 33.0

SECONDARY outcome

Timeframe: 1 year and 8 months

Population: Participants evaluable for adverse events. Participants are not being evaluated based on their post-operative treatment option. Two options are provided to the participants in order to best treat them based on the nature of their disease.

Number of participants with clinically significant congestive heart failure (CHF) as determined by established medical practices.

Outcome measures

Measure

Treatment Arm n=23 Participants Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care.

Number of Participants With Congestive Heart Failure

0 Participants

SECONDARY outcome

Timeframe: 63 months

Population: Subjects evaluable for response. Participants are not being evaluated based on their post-operative treatment option. Two options are provided to the participants in order to best treat them based on the nature of their disease.

Disease-free survival (DFS) is defined for the participants who undergo surgery, as the duration of time from surgery until ipsilateral local-regional, contralateral or distant invasive recurrence or death from any cause; in the absence of an event, DFS will be censored at the date last know alive and free from recurrence.

Outcome measures

Measure

Treatment Arm n=21 Participants Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care.

Median Disease Free Survival

NA months Less than 50% recurrence at the time of data extraction, so median DFS not reached. It is not possible to calculate the lower limit of the confidence interval.

SECONDARY outcome

Timeframe: 63 months

Population: Subjects evaluable for response. Two options are provided to the participants in order to best treat them based on the nature of their disease.

Time to treatment failure (TTF) will be defined among all participants, as the duration of time from treatment initiation to a DFS event or progressive disease during preoperative therapy or treatment disease that is not surgically resectable; in the absence of an event, TTF will be censored at the date last know alive and free from recurrence or progression.

Outcome measures

Measure

Treatment Arm n=21 Participants Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care.

Median Time to Treatment Failure

NA months Less than 50% recurrence at the time of data extraction, so median TTF not reached. Participants are not being evaluated based on their post-operative treatment option. It is not possible to calculate the lower limit of the confidence interval.

SECONDARY outcome

Timeframe: 63 months

Population: Subjects evaluable for response. Two options are provided to the participants in order to best treat them based on the nature of their disease.

Overall survival (OS) will be defined among all participants, as the duration of time from treatment initiation to death from any cause, or is censored at date last known alive. Post-surgery OS will be defined among the participants who undergo surgery, as the duration of time from treatment initiation to death from any cause, or is censored at date last known alive.

Outcome measures

Measure

Treatment Arm n=21 Participants Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care.

Median Overall Survival

NA months Less than 50% recurrence at the time of data extraction, so median OS not reached. Participants are not being evaluated based on their post-operative treatment option. It is not possible to calculate the lower limit of the confidence interval.

SECONDARY outcome

Timeframe: 18 Weeks

Population: No samples collected since very few patients had residual disease and sample size would be too small for any meaningful analysis.

Pathologic complete response (pCR) is defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative treatment. Participants whose disease is not surgically resectable following preoperative treatment are considered as not having pCR. PAM50 analysis was performed on the biopsy specimen taken on day 1.

Participants' pCR was tabulated according to the intrinsic subtype and the association of intrinsic subtype (Estrogen receptor 2 - enriched vs. other) with pCR was assessed using Fisher's exact test.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 18 Weeks

Population: No samples collected since very few patients had residual disease and sample size would be too small for any meaningful analysis.

Residual Disease Rate is the percentage of participants who do not achieve Pathologic complete response (pCR) by the end of preoperative treatment. pCR is defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative treatment. Residual disease within the breast at time of mastectomy was assessed by microarray analysis. Residual disease rate was reported by intrinsic subtype identified using day 1 RNAseq analysis.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 18 Weeks

Population: Subjects evaluable for response. Two options are provided to the participants in order to best treat them based on the nature of their disease.

Tumor RNA expression from pre-treatment (Day 1) and on-treatment (Day 8) biopsies were evaluated to see if the expression profiles had predictive accuracy of pCR. pCR is defined as absence of invasive carcinoma within the breast and axillary lymph nodes following preoperative treatment. Participants whose disease is not surgically resectable following preoperative treatment are considered as not having pCR. The biopsies were analyzed by differential expression analysis using standard procedures in R package, limma. A predictive Random Forest model was trained using leave-pair-out-cross-validation with the 80 genes most associated with pCR and/or non-pCR. This model gives an accuracy rate, which indicates the percentage of time that the gene profile predicts pCR or non-pCR for both the pre-treatment and on-treatment profiles. An increase in accuracy for the on-treatment profile would indicate an adaptive response within the tumor associated with resistance to HER2 directed therapies.

Outcome measures

Measure	Treatment Arm n=21 Participants Run in phase: Trastuzumab IV 4 mg/kg, Pertuzumab IV 840 mg (Day 1, Week 1) Pre-op phase: Trastuzumab IV 2 mg/kg weekly, Paclitaxel 80 mg/m2 IV weekly (beginning on Day 8, Week 2) x 16 doses. Starting Day 21 (week 4) continue trastuzumab and paclitaxel as above and add Pertuzumab 420 mg IV every 3 weeks during 16 doses of paclitaxel administration. After completing 16 doses of Paclitaxel, Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery Modified Radical Mastectomy Post-Operative Treatment (Two Options): Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy Post-mastectomy radiation therapy to the chest wall and regional lymph nodes and endocrine therapy administered to participants by standard of care.
Predictive Accuracy Rate of Pre-Treatment Versus On-Treatment Tumor Biopsy RNA Sequencing Profiles Day 1 Biopsy	50 percent accuracy
Predictive Accuracy Rate of Pre-Treatment Versus On-Treatment Tumor Biopsy RNA Sequencing Profiles Day 8 Biopsy	90 percent accuracy

SECONDARY outcome

Timeframe: 18 weeks

Population: Data was not collected due to a lack of clinical research funding.

Residual cancer burden is calculated an then categorized based on the methods described in the following: Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after neoadjuvant chemotherapy. J Clin Oncol 2007;25(28): 4414-22.

This method uses tumor size, the proportion of that tumor that is invasive carcinoma, the number of axillary lymph nodes containing metastatic carcinoma and the diameter of the largest metastasis in an axillary lymph node. These parameters are combined in a formula that outputs a RCB index. This index is divided into 4 categories: RCB-0, RCB-I, RCB-II, and RCB-III. The previous categories are in order of increasing severity of RCB.

Biopsy/blood will be collected on day 1 and day 8 of therapy for analysis of circulating biomarkers, including ctDNA.

Associations between change in ctDNA during therapy and residual cancer burden at the time of definitive surgery will be evaluated.

Outcome measures

Outcome data not reported

Adverse Events

Treatment Arm

Serious events: 6 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Measure	Treatment Arm n=23 participants at risk Pre-op phase: Trastuzumab: IV 4mg/kg/first dose, then IV 2mg/kg weekly. Pertuzumab: IV 840mg/first dose, then IV 420mg every 3 weeks Paclitaxel: IV 80mg/m2 weekly x 16 doses Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery. Surgery: Modified Radical Mastectomy Post-Operative Treatment: Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy All patients should also complete radiation therapy.
Blood and lymphatic system disorders Febrile neutropenia	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Diarrhea	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Alkaline phosphatase increased	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Neutrophil count decreased	13.0% 3/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.

Other adverse events

Measure	Treatment Arm n=23 participants at risk Pre-op phase: Trastuzumab: IV 4mg/kg/first dose, then IV 2mg/kg weekly. Pertuzumab: IV 840mg/first dose, then IV 420mg every 3 weeks Paclitaxel: IV 80mg/m2 weekly x 16 doses Trastuzumab (6 mg/kg IV) and Pertuzumab 420 mg IV may be continued every 3 weeks until surgery. Surgery: Modified Radical Mastectomy Post-Operative Treatment: Option 1: Adriamycin 60 mg/m2 IV and Cyclophosphamide 600 mg/m2 IV every 2-3 weeks x 4 cycles. Followed by Trastuzumab 8 mg/kg and Pertuzumab 840 IV load; followed by Trastuzumab 6 mg/kg every and Pertuzumab 420 mg IV every 3 weeks to complete 12 months of HER2-directed therapy Option 2: Continue Trastuzumab 6 mg/kg and Pertuzumab 420 mg every 3 weeks to complete 12 months of HER2-directed therapy All patients should also complete radiation therapy.
Blood and lymphatic system disorders Anemia	21.7% 5/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Blood and lymphatic system disorders Febrile neutropenia	13.0% 3/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Blood and lymphatic system disorders Lymph node pain	13.0% 3/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Ear and labyrinth disorders Ear pain	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, specify	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Eye disorders Blurred vision	17.4% 4/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Eye disorders Eye disorders - Other, specify	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Abdominal pain	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Bloating	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Cheilitis	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Constipation	17.4% 4/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Diarrhea	82.6% 19/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Dry mouth	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Dyspepsia	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Gastroesophageal reflux disease	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Hemorrhoids	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Mucositis oral	43.5% 10/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Nausea	47.8% 11/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Rectal hemorrhage	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
General disorders and administration site conditions Edema limbs	13.0% 3/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
General disorders and administration site conditions Edema trunk	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
General disorders and administration site conditions Fatigue	87.0% 20/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
General disorders and administration site conditions Fever	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
General disorders and administration site conditions Flu like symptoms	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
General disorders and administration site conditions Gait disturbance	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
General disorders and administration site conditions Infusion related reaction	21.7% 5/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
General disorders and administration site conditions Localized edema	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
General disorders and administration site conditions Non-cardiac chest pain	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
General disorders and administration site conditions Pain	13.0% 3/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Hepatobiliary disorders Hepatobiliary disorders - Other, specify	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Immune system disorders Allergic reaction	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Infections and infestations Eye infection	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Infections and infestations Paronychia	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Infections and infestations Sinusitis	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Infections and infestations Skin infection	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Infections and infestations Upper respiratory infection	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Infections and infestations Urinary tract infection	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Infections and infestations Infections and infestations - Other, specify	13.0% 3/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Injury, poisoning and procedural complications Dermatitis radiation	13.0% 3/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Alanine aminotransferase increased	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Alkaline phosphatase increased	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Aspartate aminotransferase increased	13.0% 3/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Creatinine increased	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Ejection fraction decreased	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Investigations Neutrophil count decreased	17.4% 4/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Metabolism and nutrition disorders Anorexia	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Metabolism and nutrition disorders Dehydration	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Metabolism and nutrition disorders Hyperglycemia	21.7% 5/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Metabolism and nutrition disorders Hypoalbuminemia	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Metabolism and nutrition disorders Hypokalemia	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Metabolism and nutrition disorders Hypomagnesemia	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Musculoskeletal and connective tissue disorders Arthralgia	17.4% 4/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Musculoskeletal and connective tissue disorders Back pain	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Musculoskeletal and connective tissue disorders Bone pain	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Musculoskeletal and connective tissue disorders Growth suppression	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Musculoskeletal and connective tissue disorders Myalgia	13.0% 3/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Musculoskeletal and connective tissue disorders Neck pain	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Musculoskeletal and connective tissue disorders Pain in extremity	21.7% 5/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Nervous system disorders Cognitive disturbance	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Nervous system disorders Dizziness	21.7% 5/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Nervous system disorders Dysgeusia	30.4% 7/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Nervous system disorders Extrapyramidal disorder	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Nervous system disorders Facial muscle weakness	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Nervous system disorders Headache	30.4% 7/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Nervous system disorders Movements involuntary	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Nervous system disorders Peripheral motor neuropathy	21.7% 5/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Nervous system disorders Peripheral sensory neuropathy	65.2% 15/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Psychiatric disorders Agitation	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Psychiatric disorders Anxiety	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Psychiatric disorders Depression	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Psychiatric disorders Insomnia	26.1% 6/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Psychiatric disorders Psychiatric disorders - Other, specify	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Renal and urinary disorders Acute kidney injury	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Renal and urinary disorders Urinary incontinence	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Renal and urinary disorders Urinary urgency	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Reproductive system and breast disorders Breast pain	13.0% 3/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Reproductive system and breast disorders Vaginal discharge	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Reproductive system and breast disorders Vaginal dryness	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Reproductive system and breast disorders Vaginal inflammation	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Reproductive system and breast disorders Reproductive system and breast disorders - Other, specify	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Cough	13.0% 3/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Dyspnea	17.4% 4/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Epistaxis	30.4% 7/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Nasal congestion	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Postnasal drip	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Sore throat	13.0% 3/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Tracheal fistula	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Voice alteration	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other, specify	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Alopecia	39.1% 9/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Dry skin	17.4% 4/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Erythema multiforme	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Hyperhidrosis	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Nail discoloration	13.0% 3/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Nail loss	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Nail ridging	13.0% 3/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Periorbital edema	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Pruritus	21.7% 5/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Rash acneiform	26.1% 6/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Rash maculo-papular	43.5% 10/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Urticaria	8.7% 2/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	26.1% 6/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Vascular disorders Hot flashes	17.4% 4/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Vascular disorders Lymphedema	13.0% 3/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.
Vascular disorders Thromboembolic event	4.3% 1/23 • 63 Months Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. Remaining AEs are classified as Other AEs (OAE). Maximum grade toxicity by type was calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term. Participants are not being evaluated based on their post-operative treatment option.

Additional Information

Beth Overmoyer, MD, FACP

Dana-Farber Cancer Institute

Phone: 617.632.3800

Email: beth_overmoyer@dfci.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place