Trial Outcomes & Findings for To Reduce the Use of Chemotherapy in Postmenopausal Patients With ER-positive and HER2-positive Breast Cancer (TOUCH) (NCT NCT03644186)

NCT ID: NCT03644186

Last Updated: 2024-12-13

Results Overview

Pathological complete response (pCR) is defined as absence of invasive tumour cells in the breast and in the axillary lymph nodes at the time of surgery (ypT0/ypTis ypN0) determined from the local histopathologic evaluation according to the American Joint Committee on Cancer Staging Manual. The presence of in situ cancer after trial treatment in the absence of residual invasive disease constitutes a pCR.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 147 participants
• Primary outcome timeframe: Assessed within 30 days of the time of breast surgery after completion of a treatment period of up to 16 weeks; up to 21 weeks. If the patient does not undergo surgery, assessment will occur within 30 days after all treatment is stopped; up to 30 weeks.
• Results posted on: 2024-12-13

Participant Flow

The TOUCH study was activated on 4 October 2018. The first patient was enrolled on 16 April 2019. The protocol was updated (18 February 2020) to relax the eligibility criteria in order to increase the accrual rate; expanded from women greater than or equal to 65 to postmenopausal patients. The last patient was enrolled on 28 July 2022. The final accrual was 147 patients (target 144) in 37 centers in 4 countries. Out of 147 randomized patients 2 patients did not start any protocol treatment.

Participant milestones

Measure	Paclitaxel Plus Trastuzumab and Pertuzumab Receiving paclitaxel 80mg/m2 i.v. on day 1, 8, 15 every 28 days for 4 cycles, trastuzumab 600mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for a total of 5 doses. Paclitaxel: Chemotherapy plus HER2 Blockade Trastuzumab: Chemotherapy plus HER2 Blockade Pertuzumab: Chemotherapy plus HER2 Blockade	Palbociclib Plus Letrozole Plus Trastuzumab and Pertuzumab Receiving palbociclib 125 mg/day orally for 21 days followed by 7 day's rest, for four 28 day cycles, letrozole 2.5 mg/day orally for 16 weeks and trastuzumab 600 mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for 5 doses. Palbociclib: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Letrozole: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Trastuzumab: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Pertuzumab: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade
Overall Study STARTED	74	73
Overall Study COMPLETED	73	72
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Paclitaxel Plus Trastuzumab and Pertuzumab Receiving paclitaxel 80mg/m2 i.v. on day 1, 8, 15 every 28 days for 4 cycles, trastuzumab 600mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for a total of 5 doses. Paclitaxel: Chemotherapy plus HER2 Blockade Trastuzumab: Chemotherapy plus HER2 Blockade Pertuzumab: Chemotherapy plus HER2 Blockade	Palbociclib Plus Letrozole Plus Trastuzumab and Pertuzumab Receiving palbociclib 125 mg/day orally for 21 days followed by 7 day's rest, for four 28 day cycles, letrozole 2.5 mg/day orally for 16 weeks and trastuzumab 600 mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for 5 doses. Palbociclib: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Letrozole: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Trastuzumab: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Pertuzumab: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Paclitaxel Plus Trastuzumab and Pertuzumab n=74 Participants Receiving paclitaxel 80mg/m2 i.v. on day 1, 8, 15 every 28 days for 4 cycles, trastuzumab 600mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for a total of 5 doses. Paclitaxel: Chemotherapy plus HER2 Blockade Trastuzumab: Chemotherapy plus HER2 Blockade Pertuzumab: Chemotherapy plus HER2 Blockade	Palbociclib Plus Letrozole Plus Trastuzumab and Pertuzumab n=73 Participants Receiving palbociclib 125 mg/day orally for 21 days followed by 7 day's rest, for four 28 day cycles, letrozole 2.5 mg/day orally for 16 weeks and trastuzumab 600 mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for 5 doses. Palbociclib: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Letrozole: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Trastuzumab: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Pertuzumab: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade	Total n=147 Participants Total of all reporting groups
Age, Customized >=65 years	53 Participants n=74 Participants	50 Participants n=73 Participants	103 Participants n=147 Participants
Sex: Female, Male Female	74 Participants n=74 Participants	73 Participants n=73 Participants	147 Participants n=147 Participants
Sex: Female, Male Male	0 Participants n=74 Participants	0 Participants n=73 Participants	0 Participants n=147 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Belgium	10 participants n=74 Participants	11 participants n=73 Participants	21 participants n=147 Participants
Region of Enrollment Italy	44 participants n=74 Participants	41 participants n=73 Participants	85 participants n=147 Participants
Region of Enrollment France	7 participants n=74 Participants	6 participants n=73 Participants	13 participants n=147 Participants
Region of Enrollment Switzerland	13 participants n=74 Participants	15 participants n=73 Participants	28 participants n=147 Participants
Age, Customized <65 years	21 Participants n=74 Participants	23 Participants n=73 Participants	44 Participants n=147 Participants

PRIMARY outcome

Timeframe: Assessed within 30 days of the time of breast surgery after completion of a treatment period of up to 16 weeks; up to 21 weeks. If the patient does not undergo surgery, assessment will occur within 30 days after all treatment is stopped; up to 30 weeks.

Pathological complete response (pCR) is defined as absence of invasive tumour cells in the breast and in the axillary lymph nodes at the time of surgery (ypT0/ypTis ypN0) determined from the local histopathologic evaluation according to the American Joint Committee on Cancer Staging Manual. The presence of in situ cancer after trial treatment in the absence of residual invasive disease constitutes a pCR.

Outcome measures

Measure	Paclitaxel Plus Trastuzumab and Pertuzumab n=73 Participants Receiving paclitaxel 80mg/m2 i.v. on day 1, 8, 15 every 28 days for 4 cycles, trastuzumab 600mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for a total of 5 doses. Paclitaxel: Chemotherapy plus HER2 Blockade Trastuzumab: Chemotherapy plus HER2 Blockade Pertuzumab: Chemotherapy plus HER2 Blockade	Palbociclib Plus Letrozole Plus Trastuzumab and Pertuzumab n=72 Participants Receiving palbociclib 125 mg/day orally for 21 days followed by 7 day's rest, for four 28 day cycles, letrozole 2.5 mg/day orally for 16 weeks and trastuzumab 600 mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for 5 doses. Palbociclib: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Letrozole: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Trastuzumab: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Pertuzumab: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade
Pathological Complete Response (pCR)	24 Participants	24 Participants

SECONDARY outcome

Timeframe: Assessed within 30 days of the time of breast surgery after completion of a treatment period of up to 16 weeks; up to 21 weeks. If the patient does not undergo surgery, assessment will occur within 30 days after all treatment is stopped; up to 30 weeks.

Defined as the absence of invasive tumour cells in the breast at the time of surgery (ypT0/ypTis) determined from the local histopathologic evaluation according to the American Joint Committee on Cancer Staging Manual..

Outcome measures

Measure	Paclitaxel Plus Trastuzumab and Pertuzumab n=73 Participants Receiving paclitaxel 80mg/m2 i.v. on day 1, 8, 15 every 28 days for 4 cycles, trastuzumab 600mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for a total of 5 doses. Paclitaxel: Chemotherapy plus HER2 Blockade Trastuzumab: Chemotherapy plus HER2 Blockade Pertuzumab: Chemotherapy plus HER2 Blockade	Palbociclib Plus Letrozole Plus Trastuzumab and Pertuzumab n=72 Participants Receiving palbociclib 125 mg/day orally for 21 days followed by 7 day's rest, for four 28 day cycles, letrozole 2.5 mg/day orally for 16 weeks and trastuzumab 600 mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for 5 doses. Palbociclib: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Letrozole: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Trastuzumab: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Pertuzumab: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade
Pathological Complete Response (pCR) in the Breast	26 Participants	25 Participants

SECONDARY outcome

Timeframe: Tumor assessments were performed by ultrasound and mammography at screening (prior to treatment start), and before surgery; measurements by caliper were assessed at the same time points and at the end of cycle 2 (28 days/cycle), approximately 56 days.

The number of patients with partial or complete response measured physically by caliper and by ultrasound and mammography. Response was assessed using World Health Organization tumor measurement and response criteria.

Complete response (CR) - The disappearance of all known disease. Partial response (PR) - A 50% or more decrease in total tumor size, i.e., the sum of the products of the maximal diameter (MD) and the corresponding largest perpendicular diameter (LPD) of the lesions which have been measured to determine the effect of therapy. In addition, there can be no appearance of new lesions or progression of any lesion.

Stable disease (SD) - Neither a 50% decrease in total tumor size, nor a 25% increase in the size of one or more measurable lesions has been determined.

Progressive disease (PD) - An increase of least 25% in total tumor size relative to the smallest size measured during the trial.

Outcome measures

Measure	Paclitaxel Plus Trastuzumab and Pertuzumab n=73 Participants Receiving paclitaxel 80mg/m2 i.v. on day 1, 8, 15 every 28 days for 4 cycles, trastuzumab 600mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for a total of 5 doses. Paclitaxel: Chemotherapy plus HER2 Blockade Trastuzumab: Chemotherapy plus HER2 Blockade Pertuzumab: Chemotherapy plus HER2 Blockade	Palbociclib Plus Letrozole Plus Trastuzumab and Pertuzumab n=72 Participants Receiving palbociclib 125 mg/day orally for 21 days followed by 7 day's rest, for four 28 day cycles, letrozole 2.5 mg/day orally for 16 weeks and trastuzumab 600 mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for 5 doses. Palbociclib: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Letrozole: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Trastuzumab: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Pertuzumab: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade
Objective Response Objective response - complete response	35 Participants	38 Participants
Objective Response Objective response - partial response	17 Participants	19 Participants
Objective Response Objective response - stable disease	4 Participants	4 Participants
Objective Response Objective response - progressive disease	3 Participants	2 Participants
Objective Response Objective response - not evaluable	14 Participants	9 Participants

SECONDARY outcome

Timeframe: From randomization until completion of study, up to 20 months

Defined as the number of patients undergoing BCS, divided by the number of patients in the assessable population (subset of the randomized population with RBsig status successfully determined who received at least 1 dose of medication).

Outcome measures

Measure	Paclitaxel Plus Trastuzumab and Pertuzumab n=73 Participants Receiving paclitaxel 80mg/m2 i.v. on day 1, 8, 15 every 28 days for 4 cycles, trastuzumab 600mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for a total of 5 doses. Paclitaxel: Chemotherapy plus HER2 Blockade Trastuzumab: Chemotherapy plus HER2 Blockade Pertuzumab: Chemotherapy plus HER2 Blockade	Palbociclib Plus Letrozole Plus Trastuzumab and Pertuzumab n=72 Participants Receiving palbociclib 125 mg/day orally for 21 days followed by 7 day's rest, for four 28 day cycles, letrozole 2.5 mg/day orally for 16 weeks and trastuzumab 600 mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for 5 doses. Palbociclib: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Letrozole: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Trastuzumab: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Pertuzumab: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade
Rate of Breast Conserving Surgery (BCS)	49 Participants	59 Participants

Adverse Events

Paclitaxel Plus Trastuzumab and Pertuzumab

Serious events: 23 serious events

Other events: 68 other events

Deaths: 0 deaths

Palbociclib Plus Letrozole Plus Trastuzumab and Pertuzumab

Serious events: 39 serious events

Other events: 69 other events

Deaths: 0 deaths

Serious adverse events

Measure	Paclitaxel Plus Trastuzumab and Pertuzumab n=73 participants at risk Receiving paclitaxel 80mg/m2 i.v. on day 1, 8, 15 every 28 days for 4 cycles, trastuzumab 600mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for a total of 5 doses. Paclitaxel: Chemotherapy plus HER2 Blockade Trastuzumab: Chemotherapy plus HER2 Blockade Pertuzumab: Chemotherapy plus HER2 Blockade	Palbociclib Plus Letrozole Plus Trastuzumab and Pertuzumab n=72 participants at risk Receiving palbociclib 125 mg/day orally for 21 days followed by 7 day's rest, for four 28 day cycles, letrozole 2.5 mg/day orally for 16 weeks and trastuzumab 600 mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for 5 doses. Palbociclib: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Letrozole: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Trastuzumab: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Pertuzumab: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade
Investigations Neutrophil count decreased	6.8% 5/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	43.1% 31/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Gastrointestinal disorders Diarrhea	11.0% 8/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	8.3% 6/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Infections and infestations Infections	0.00% 0/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	2.8% 2/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Skin and subcutaneous tissue disorders Skin and cutaneous disorders	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Cardiac disorders Left ventricular systolic dysfunction	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	2.8% 2/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Vascular disorders Hypertension	2.7% 2/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	5.6% 4/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Infections and infestations Ejection fraction decreased	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	1.4% 1/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Investigations Alanine aminotransferase increased	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	4.2% 3/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Investigations Aspartate aminotransferase increased	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	4.2% 3/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Skin and subcutaneous tissue disorders Alopecia	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Investigations Blood bilirubin increased	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Musculoskeletal and connective tissue disorders Bone pain	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Eye disorders Eye disorders - Other, specify	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
General disorders Fatigue	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Injury, poisoning and procedural complications Hip fracture	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Metabolism and nutrition disorders Hypokalemia	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Gastrointestinal disorders Ileal obstruction	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Musculoskeletal and connective tissue disorders Muscle cramp	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Nervous system disorders Peripheral sensory neuropathy	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Gastrointestinal disorders Small intestinal obstruction	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Investigations White blood cell decreased	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	1.4% 1/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Renal and urinary disorders Acute kidney injury	0.00% 0/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	1.4% 1/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.

Other adverse events

Measure	Paclitaxel Plus Trastuzumab and Pertuzumab n=73 participants at risk Receiving paclitaxel 80mg/m2 i.v. on day 1, 8, 15 every 28 days for 4 cycles, trastuzumab 600mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for a total of 5 doses. Paclitaxel: Chemotherapy plus HER2 Blockade Trastuzumab: Chemotherapy plus HER2 Blockade Pertuzumab: Chemotherapy plus HER2 Blockade	Palbociclib Plus Letrozole Plus Trastuzumab and Pertuzumab n=72 participants at risk Receiving palbociclib 125 mg/day orally for 21 days followed by 7 day's rest, for four 28 day cycles, letrozole 2.5 mg/day orally for 16 weeks and trastuzumab 600 mg s.c. every 3 weeks for a total of 5 doses and pertuzumab 840 mg i.v. loading dose followed by 420 mg i.v. every 3 weeks for 5 doses. Palbociclib: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Letrozole: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Trastuzumab: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade Pertuzumab: CDK Inhibition plus Hormonal Therapy plus HER2 Blockade
Investigations Neutrophil count decreased	16.4% 12/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	31.9% 23/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Blood and lymphatic system disorders Anemia	49.3% 36/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	48.6% 35/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Investigations Platelet count decreased	2.7% 2/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	38.9% 28/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Gastrointestinal disorders Nausea	26.0% 19/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	22.2% 16/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Gastrointestinal disorders Diarrhea	61.6% 45/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	65.3% 47/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Vascular disorders Thromboembolic event	2.7% 2/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	1.4% 1/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Infections and infestations Infections	24.7% 18/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	19.4% 14/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Skin and subcutaneous tissue disorders Skin and cutaneous disorders	41.1% 30/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	30.6% 22/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Vascular disorders Hypertension	9.6% 7/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	1.4% 1/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Investigations Ejection fraction decreased	5.5% 4/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	2.8% 2/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Hepatobiliary disorders Hepatobiliary disorder	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Cardiac disorders Palpitations	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Cardiac disorders Ventricular arrhythmia	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Gastrointestinal disorders Abdominal pain	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Gastrointestinal disorders Mucositis oral	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	5.6% 4/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Gastrointestinal disorders Stomach pain	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
General disorders Fatigue	11.0% 8/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	2.8% 2/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Immune system disorders Allergic reaction	11.0% 8/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Injury, poisoning and procedural complications Infusion related reaction	8.2% 6/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Investigations Alanine aminotransferase increased	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	4.2% 3/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Investigations Aspartate aminotransferase increased	0.00% 0/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	2.8% 2/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Investigations White blood cell decreased	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	4.2% 3/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Metabolism and nutrition disorders Hypoalbuminemia	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Metabolism and nutrition disorders Hypokalemia	0.00% 0/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	1.4% 1/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Musculoskeletal and connective tissue disorders Myalgia	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Nervous system disorders Peripheral sensory neuropathy	6.8% 5/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Psychiatric disorders Depression	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Reproductive system and breast disorders Vaginal dryness	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Respiratory, thoracic and mediastinal disorders Cough	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Skin and subcutaneous tissue disorders Alopecia	4.1% 3/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	1.4% 1/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Vascular disorders Phlebitis	1.4% 1/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Gastrointestinal disorders Anal fissure	0.00% 0/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	1.4% 1/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Gastrointestinal disorders Anal mucositis	0.00% 0/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	1.4% 1/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Gastrointestinal disorders Constipation	0.00% 0/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	2.8% 2/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Gastrointestinal disorders Vomiting	0.00% 0/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	1.4% 1/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Investigations Conjunctivitis	0.00% 0/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	1.4% 1/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Investigations GGT increased	0.00% 0/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	1.4% 1/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Investigations Weight loss	0.00% 0/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	1.4% 1/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Nervous system disorders Dysgeusia	0.00% 0/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	1.4% 1/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Nervous system disorders Headache	0.00% 0/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	1.4% 1/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Renal and urinary disorders Acute kidney injury	0.00% 0/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	0.00% 0/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.
Vascular disorders Hot flashes	0.00% 0/73 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.	1.4% 1/72 • Assessed at the end of every 4-week cycle until the end of trial treatment prior to surgery; up to 20 weeks. Only serious adverse events were assessed 30 days after end of treatment; up to 21 weeks. The severity and causality will be classified according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5. The CTCAE is available for downloading on the internet at http://evs.nci.nih.gov/ftp1/CTCAE/About.html. For this trial, Grade 1s were not collected for non-targeted adverse events and hence are not included in the reporting of Other (not including serious) adverse event table.

Additional Information

Dr. Heidi Roschitzki

ETOP IBCSG Partners Foundation

Phone: +41 31 511 94 00

Email: TOUCH-monitoring@etop.ibcsg.org

Results disclosure agreements

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