Trial Outcomes & Findings for Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician's Choice in Participants With HR+/HER2- Metastatic Breast Cancer (NCT NCT03901339)

Last Updated: 2024-10-21

Results Overview

PFS was defined as the time from the date of randomization to the date of the first documentation of disease progression or death (whichever occurred first) according to BICR using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Disease progression was defined as an increase of greater than 20% in the sum of the longest diameter (LD) of target lesions and a 5 mm absolute increase, taking as a reference the smallest sum LD recorded since the baseline assessment or the appearance of new non-target lesions. PFS was estimated using Kaplan-Meier estimate.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

543 participants

Primary outcome timeframe

Up to 42.8 months

Results posted on

2024-10-21

Participant Flow

Participants were enrolled at study sites in Belgium, Canada, France, Germany, Italy, the Netherlands, Spain, the United Kingdom, and the United States.

776 participants were screened.

Participant milestones

Participant milestones
Measure	Sacituzumab Govitecan Participants received sacituzumab govitecan 10 mg/kg of body weight, administered as a slow intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, occurrence of unacceptable adverse events (AEs), or another treatment discontinuation criterion was met (up to 40.1 months).	Treatment of Physician's Choice (TPC) Participants received TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent treatment that was determined by the investigator before participant randomization until progression of disease, occurrence of unacceptable adverse events (AEs), or another treatment discontinuation criterion was met. Dosing per National Comprehensive Cancer Network (NCCN) guidelines (with dose modifications for if toxic) * Eribulin was administered IV at a dose 1.4 mg/m\^2 at North American sites and 1.2 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle (up to 22.5 months). * Capecitabine 1000 to 1250 mg/m\^2 was administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period (up to 12.9 months). * Gemcitabine 800 to 1200 mg/m\^2 was administered IV on Days 1, 8, and 15 of a 28-day cycle (up to 22.3 months). * Vinorelbine 25 mg/m\^2 was administered as a weekly IV injection (up to 8.1 months). Vinorelbine was not allowed as TPC for any participant with Grade 2 neuropathy.
Overall Study STARTED	272	271
Overall Study Received at Least 1 Dose of Study Drug	268	249
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	272	271

Reasons for withdrawal

Reasons for withdrawal
Measure	Sacituzumab Govitecan Participants received sacituzumab govitecan 10 mg/kg of body weight, administered as a slow intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, occurrence of unacceptable adverse events (AEs), or another treatment discontinuation criterion was met (up to 40.1 months).	Treatment of Physician's Choice (TPC) Participants received TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent treatment that was determined by the investigator before participant randomization until progression of disease, occurrence of unacceptable adverse events (AEs), or another treatment discontinuation criterion was met. Dosing per National Comprehensive Cancer Network (NCCN) guidelines (with dose modifications for if toxic) * Eribulin was administered IV at a dose 1.4 mg/m\^2 at North American sites and 1.2 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle (up to 22.5 months). * Capecitabine 1000 to 1250 mg/m\^2 was administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period (up to 12.9 months). * Gemcitabine 800 to 1200 mg/m\^2 was administered IV on Days 1, 8, and 15 of a 28-day cycle (up to 22.3 months). * Vinorelbine 25 mg/m\^2 was administered as a weekly IV injection (up to 8.1 months). Vinorelbine was not allowed as TPC for any participant with Grade 2 neuropathy.
Overall Study Death	220	192
Overall Study Informed consent withdrawn	13	40
Overall Study Sponsor request	30	23
Overall Study Reason not specified	5	7
Overall Study Lost to Follow-up	4	7
Overall Study Covid19	0	2

Baseline Characteristics

Study of Sacituzumab Govitecan-hziy Versus Treatment of Physician's Choice in Participants With HR+/HER2- Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sacituzumab Govitecan n=272 Participants Participants received sacituzumab govitecan 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met (up to 40.1 months).	Treatment of Physician's Choice (TPC) n=271 Participants Participants received TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent treatment that was determined by the investigator before participant randomization until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met. Dosing per NCCN guidelines (with dose modifications for if toxic) * Eribulin was administered IV at a dose 1.4 mg/m\^2 at North American sites and 1.2 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle (up to 22.5 months). * Capecitabine 1000 to 1250 mg/m\^2 was administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period (up to 12.9 months). * Gemcitabine 800 to 1200 mg/m\^2 was administered IV on Days 1, 8, and 15 of a 28-day cycle (up to 22.3 months). * Vinorelbine 25 mg/m\^2 was administered as a weekly IV injection (up to 8.1 months). Vinorelbine was not allowed as TPC for any participant with Grade 2 neuropathy.	Total~(N=543) n=543 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	199 Participants n=5 Participants	204 Participants n=7 Participants	403 Participants n=5 Participants
Age, Categorical >=65 years	73 Participants n=5 Participants	67 Participants n=7 Participants	140 Participants n=5 Participants
Age, Continuous	57 years STANDARD_DEVIATION 11.5 • n=5 Participants	56 years STANDARD_DEVIATION 10.4 • n=7 Participants	56 years STANDARD_DEVIATION 11.0 • n=5 Participants
Sex: Female, Male Female	270 Participants n=5 Participants	268 Participants n=7 Participants	538 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	12 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	222 Participants n=5 Participants	204 Participants n=7 Participants	426 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	44 Participants n=5 Participants	55 Participants n=7 Participants	99 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	184 Participants n=5 Participants	178 Participants n=7 Participants	362 Participants n=5 Participants
Race/Ethnicity, Customized Race · Unknown or Not Reported	69 Participants n=5 Participants	70 Participants n=7 Participants	139 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black or African American	8 Participants n=5 Participants	13 Participants n=7 Participants	21 Participants n=5 Participants
Race/Ethnicity, Customized Race · Asian	11 Participants n=5 Participants	5 Participants n=7 Participants	16 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other or More Than One Race	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Race · Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	115 Participants n=5 Participants	113 Participants n=7 Participants	228 Participants n=5 Participants
Region of Enrollment France	64 Participants n=5 Participants	73 Participants n=7 Participants	137 Participants n=5 Participants
Region of Enrollment Spain	35 Participants n=5 Participants	34 Participants n=7 Participants	69 Participants n=5 Participants
Region of Enrollment Germany	20 Participants n=5 Participants	26 Participants n=7 Participants	46 Participants n=5 Participants
Region of Enrollment Belgium	16 Participants n=5 Participants	9 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment Italy	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Region of Enrollment United Kingdom	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Region of Enrollment Netherlands	6 Participants n=5 Participants	2 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment Canada	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 42.8 months

Population: The ITT Population included all participants who were randomized, regardless of whether they received study treatment or not.

Outcome measures

Outcome measures
Measure	Sacituzumab Govitecan n=272 Participants Participants received sacituzumab govitecan 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met (up to 40.1 months).	Treatment of Physician's Choice (TPC) n=271 Participants Participants received TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent treatment that was determined by the investigator before participant randomization until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met. Dosing per NCCN guidelines (with dose modifications for if toxic) * Eribulin was administered IV at a dose 1.4 mg/m\^2 at North American sites and 1.2 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle (up to 22.5 months). * Capecitabine 1000 to 1250 mg/m\^2 was administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period (up to 12.9 months). * Gemcitabine 800 to 1200 mg/m\^2 was administered IV on Days 1, 8, and 15 of a 28-day cycle (up to 22.3 months). * Vinorelbine 25 mg/m\^2 was administered as a weekly IV injection (up to 8.1 months). Vinorelbine was not allowed as TPC for any participant with Grade 2 neuropathy.
Progression-Free Survival (PFS) by Blinded Independent Central Review (BICR) Assessment	5.5 months Interval 4.2 to 6.9	4.0 months Interval 3.0 to 4.4

SECONDARY outcome

Timeframe: Up to 42.8 months

Population: Participants in the ITT Population were analyzed.

OS was defined as the time from the date of randomization to the date of death from any cause. OS was estimated using Kaplan-Meier estimate. Participants without documentation of death were censored on the date they were last known to be alive.

Outcome measures

Outcome measures
Measure	Sacituzumab Govitecan n=272 Participants Participants received sacituzumab govitecan 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met (up to 40.1 months).	Treatment of Physician's Choice (TPC) n=271 Participants Participants received TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent treatment that was determined by the investigator before participant randomization until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met. Dosing per NCCN guidelines (with dose modifications for if toxic) * Eribulin was administered IV at a dose 1.4 mg/m\^2 at North American sites and 1.2 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle (up to 22.5 months). * Capecitabine 1000 to 1250 mg/m\^2 was administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period (up to 12.9 months). * Gemcitabine 800 to 1200 mg/m\^2 was administered IV on Days 1, 8, and 15 of a 28-day cycle (up to 22.3 months). * Vinorelbine 25 mg/m\^2 was administered as a weekly IV injection (up to 8.1 months). Vinorelbine was not allowed as TPC for any participant with Grade 2 neuropathy.
Overall Survival (OS)	14.5 months Interval 13.0 to 16.0	11.2 months Interval 10.2 to 12.6

SECONDARY outcome

Timeframe: Up to 42.8 months

Population: Participants in the ITT Population with available data were analyzed.

ORR was defined as the percentage of participants who had the best overall response of either complete response (CR) or partial response (PR) that was confirmed at 4 weeks or later after initial response by BICR and LIR using RECIST 1.1. CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; PR: ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD.

Outcome measures

Outcome measures
Measure	Sacituzumab Govitecan n=272 Participants Participants received sacituzumab govitecan 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met (up to 40.1 months).	Treatment of Physician's Choice (TPC) n=271 Participants Participants received TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent treatment that was determined by the investigator before participant randomization until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met. Dosing per NCCN guidelines (with dose modifications for if toxic) * Eribulin was administered IV at a dose 1.4 mg/m\^2 at North American sites and 1.2 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle (up to 22.5 months). * Capecitabine 1000 to 1250 mg/m\^2 was administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period (up to 12.9 months). * Gemcitabine 800 to 1200 mg/m\^2 was administered IV on Days 1, 8, and 15 of a 28-day cycle (up to 22.3 months). * Vinorelbine 25 mg/m\^2 was administered as a weekly IV injection (up to 8.1 months). Vinorelbine was not allowed as TPC for any participant with Grade 2 neuropathy.
Objective Response Rate (ORR) by BICR and Local Investigator Review (LIR) Assessment ORR by BICR Assessment	21.3 percentage of participants Interval 16.6 to 26.7	14.0 percentage of participants Interval 10.1 to 18.7
Objective Response Rate (ORR) by BICR and Local Investigator Review (LIR) Assessment ORR by LIR Assessment	16.5 percentage of participants Interval 12.3 to 21.5	9.2 percentage of participants Interval 6.1 to 13.3

SECONDARY outcome

Timeframe: Up to 42.8 months

Population: Participants in the ITT Population with confirmed objective response were analyzed.

DOR was defined as the time from the date a response of CR or PR was first documented until the date of the first documentation of disease progression or date of death (whichever occurred first). DOR was analyzed based on both BICR and LIR assessments. CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; PR: ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. Disease progression was defined as an increase of greater than 20% in the sum of the LD of target lesions and a 5 mm absolute increase, taking as a reference the smallest sum LD recorded since the baseline assessment or the appearance of new non-target lesions. DOR was estimated using Kaplan-Meier estimate.

Outcome measures

Outcome measures
Measure	Sacituzumab Govitecan n=58 Participants Participants received sacituzumab govitecan 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met (up to 40.1 months).	Treatment of Physician's Choice (TPC) n=38 Participants Participants received TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent treatment that was determined by the investigator before participant randomization until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met. Dosing per NCCN guidelines (with dose modifications for if toxic) * Eribulin was administered IV at a dose 1.4 mg/m\^2 at North American sites and 1.2 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle (up to 22.5 months). * Capecitabine 1000 to 1250 mg/m\^2 was administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period (up to 12.9 months). * Gemcitabine 800 to 1200 mg/m\^2 was administered IV on Days 1, 8, and 15 of a 28-day cycle (up to 22.3 months). * Vinorelbine 25 mg/m\^2 was administered as a weekly IV injection (up to 8.1 months). Vinorelbine was not allowed as TPC for any participant with Grade 2 neuropathy.
Duration of Response (DOR) by BICR and LIR Assessment DOR by BICR Assessment	8.1 months Interval 6.7 to 8.9	5.6 months Interval 3.8 to 7.9
Duration of Response (DOR) by BICR and LIR Assessment DOR by LIR Assessment	7.0 months Interval 5.6 to 8.9	4.3 months Interval 4.2 to 6.1

SECONDARY outcome

Timeframe: Up to 42.8 months

Population: Participants in the ITT Population with available data were analyzed.

CBR was defined as the percentage of participants with the best overall response of CR, PR, or durable stable disease (duration of SD ≥ 6 months after randomization). CBR was analyzed based on both BICR and LIR assessments. CR: Disappearance of all target and non-target lesions; and normalization of tumor marker levels initially above upper limits of normal; PR: ≥30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started. PD: Disease progression was defined as an increase of greater than 20% in the sum of the LD of target lesions and a 5 mm absolute increase, taking as a reference the smallest sum LD recorded since the baseline assessment or the appearance of new non-target lesions.

Outcome measures

Outcome measures
Measure	Sacituzumab Govitecan n=272 Participants Participants received sacituzumab govitecan 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met (up to 40.1 months).	Treatment of Physician's Choice (TPC) n=271 Participants Participants received TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent treatment that was determined by the investigator before participant randomization until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met. Dosing per NCCN guidelines (with dose modifications for if toxic) * Eribulin was administered IV at a dose 1.4 mg/m\^2 at North American sites and 1.2 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle (up to 22.5 months). * Capecitabine 1000 to 1250 mg/m\^2 was administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period (up to 12.9 months). * Gemcitabine 800 to 1200 mg/m\^2 was administered IV on Days 1, 8, and 15 of a 28-day cycle (up to 22.3 months). * Vinorelbine 25 mg/m\^2 was administered as a weekly IV injection (up to 8.1 months). Vinorelbine was not allowed as TPC for any participant with Grade 2 neuropathy.
Clinical Benefit Rate (CBR) by BICR and LIR Assessment CBR by BICR Assessment	33.8 percentage of participants Interval 28.2 to 39.8	22.1 percentage of participants Interval 17.3 to 27.6
Clinical Benefit Rate (CBR) by BICR and LIR Assessment CBR by LIR Assessment	32.4 percentage of participants Interval 26.8 to 38.3	21.0 percentage of participants Interval 16.3 to 26.4

SECONDARY outcome

Timeframe: Up to 42.8 months

Population: Participants in the ITT Population were analyzed.

PFS was defined as the time from the date of randomization to the date of the first documentation of disease progression or death (whichever occurred first) according to LIR using RECIST 1.1. Disease progression was defined as an increase of greater than 20% in the sum of the LD of target lesions and a 5 mm absolute increase, taking as a reference the smallest sum LD recorded since the baseline assessment or the appearance of new non-target lesions. PFS was estimated using Kaplan-Meier estimate.

Outcome measures

Outcome measures
Measure	Sacituzumab Govitecan n=272 Participants Participants received sacituzumab govitecan 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met (up to 40.1 months).	Treatment of Physician's Choice (TPC) n=271 Participants Participants received TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent treatment that was determined by the investigator before participant randomization until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met. Dosing per NCCN guidelines (with dose modifications for if toxic) * Eribulin was administered IV at a dose 1.4 mg/m\^2 at North American sites and 1.2 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle (up to 22.5 months). * Capecitabine 1000 to 1250 mg/m\^2 was administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period (up to 12.9 months). * Gemcitabine 800 to 1200 mg/m\^2 was administered IV on Days 1, 8, and 15 of a 28-day cycle (up to 22.3 months). * Vinorelbine 25 mg/m\^2 was administered as a weekly IV injection (up to 8.1 months). Vinorelbine was not allowed as TPC for any participant with Grade 2 neuropathy.
PFS by LIR Assessment	4.3 months Interval 3.8 to 5.4	3.1 months Interval 2.7 to 4.0

SECONDARY outcome

Timeframe: Up to 37.8 months

Population: The HRQOL-Evaluable Population included all participants who had an evaluable assessment at baseline and at least 1 evaluable assessment at postbaseline visits. Participants with a baseline global health status/QOL score ≥ 10 were analyzed.

TTD was defined as the time from randomization to the first date a subject achieves 10-point deterioration from baseline in the global health status/QoL scale.The EORTC QLQ-C30 is a 30-item questionnaire to assess QoL of cancer patients. It has 5 functional scales(physical,role,emotional,cognitive, social)1 global health status scale,3 symptom scales (fatigue, nausea and vomiting, pain),and 6 single items(dyspnea, insomnia, loss of appetite, constipation, diarrhea, financial difficulties). Participant responses to global health status,'How would you rate your overall health during the past week?' (Item 29)and the QoL 'How would you rate your overall quality of life during the past week?'(Item 30)questions were scored on 7-point scale (1=very poor; 7=excellent). All scales and single-item measures range in score from 0 to 100. Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100. Higher scores for GHS show a better level of functioning.

Outcome measures

Outcome measures
Measure	Sacituzumab Govitecan n=234 Participants Participants received sacituzumab govitecan 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met (up to 40.1 months).	Treatment of Physician's Choice (TPC) n=207 Participants Participants received TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent treatment that was determined by the investigator before participant randomization until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met. Dosing per NCCN guidelines (with dose modifications for if toxic) * Eribulin was administered IV at a dose 1.4 mg/m\^2 at North American sites and 1.2 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle (up to 22.5 months). * Capecitabine 1000 to 1250 mg/m\^2 was administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period (up to 12.9 months). * Gemcitabine 800 to 1200 mg/m\^2 was administered IV on Days 1, 8, and 15 of a 28-day cycle (up to 22.3 months). * Vinorelbine 25 mg/m\^2 was administered as a weekly IV injection (up to 8.1 months). Vinorelbine was not allowed as TPC for any participant with Grade 2 neuropathy.
Time to Deterioration (TTD) of Global Health Status/Quality of Life (QoL) Scale as Measured by European Organization for Research and Treatment of Cancer Quality of Life for Cancer Patients, Core Questionnaire Version 3.0 (EORTC QLQ-C30)	4.3 months Interval 3.1 to 5.7	3.0 months Interval 2.2 to 3.9

SECONDARY outcome

Timeframe: Up to 37.8 months

Population: Participants in the HRQOL-Evaluable Population with baseline pain score ≤ 90 were analyzed.

TTD was defined as the time from randomization to the first date a subject achieves 10-point deterioration from baseline in the pain score.The EORTC QLQ-C30 is a questionnaire to assess quality of life, it is composed of 30 questions(items) resulting in 5 functional scales(physical, role, emotional, cognitive, social),1 global health status scale,3 symptom scales (fatigue, nausea and vomiting, pain),and 6 single items(dyspnea, insomnia, loss of appetite, constipation, diarrhea, financial difficulties). All of the scales and single-item measures range in score from 0 to 100. Participant responses to 2 questions about pain, 'Have you had pain' and 'Did pain interfere with your daily activities' were scored on 4-point scale (1=not at all;4=very much). Summed raw scores were standardized by linear transformation so that scores ranges from 0 to 100. Higher scores on the symptom scales indicate a higher level of symptoms (i.e. a worse state of the participant).

Outcome measures

Outcome measures
Measure	Sacituzumab Govitecan n=229 Participants Participants received sacituzumab govitecan 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met (up to 40.1 months).	Treatment of Physician's Choice (TPC) n=202 Participants Participants received TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent treatment that was determined by the investigator before participant randomization until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met. Dosing per NCCN guidelines (with dose modifications for if toxic) * Eribulin was administered IV at a dose 1.4 mg/m\^2 at North American sites and 1.2 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle (up to 22.5 months). * Capecitabine 1000 to 1250 mg/m\^2 was administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period (up to 12.9 months). * Gemcitabine 800 to 1200 mg/m\^2 was administered IV on Days 1, 8, and 15 of a 28-day cycle (up to 22.3 months). * Vinorelbine 25 mg/m\^2 was administered as a weekly IV injection (up to 8.1 months). Vinorelbine was not allowed as TPC for any participant with Grade 2 neuropathy.
TTD of Pain Score as Measured by EORTC QLQ-C30	3.8 months Interval 2.8 to 5.0	3.5 months Interval 2.8 to 5.0

SECONDARY outcome

Timeframe: Up to 37.8 months

Population: Participants in the HRQOL-Evaluable Population with baseline fatigue score ≤ 90 were analyzed.

TTD was defined as the time from randomization to the first date a subject achieves 10-point deterioration from baseline in the fatigue score.The EORTC QLQ-C30 is a questionnaire to assess quality of life, it is composed of 30 questions(items) resulting in 5 functional scales(physical, role, emotional, cognitive, social),1 global health status scale,3 symptom scales (fatigue, nausea and vomiting, pain),and 6 single items(dyspnea, insomnia, loss of appetite, constipation, diarrhea, financial difficulties).All of the scales and single-item measures range in score from 0 to 100.Participant responses to 3 questions about fatigue 'Did you need to rest', 'Have you felt weak' and 'Were you tired' were scored on a 4-point scale (1=not at all;4=very much).Summed raw scores were standardized by linear transformation so that scores ranged from 0 to 100. Higher scores on the symptom scales indicate a higher level of symptoms (i.e. a worse state of the participant).

Outcome measures

Outcome measures
Measure	Sacituzumab Govitecan n=234 Participants Participants received sacituzumab govitecan 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met (up to 40.1 months).	Treatment of Physician's Choice (TPC) n=205 Participants Participants received TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent treatment that was determined by the investigator before participant randomization until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met. Dosing per NCCN guidelines (with dose modifications for if toxic) * Eribulin was administered IV at a dose 1.4 mg/m\^2 at North American sites and 1.2 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle (up to 22.5 months). * Capecitabine 1000 to 1250 mg/m\^2 was administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period (up to 12.9 months). * Gemcitabine 800 to 1200 mg/m\^2 was administered IV on Days 1, 8, and 15 of a 28-day cycle (up to 22.3 months). * Vinorelbine 25 mg/m\^2 was administered as a weekly IV injection (up to 8.1 months). Vinorelbine was not allowed as TPC for any participant with Grade 2 neuropathy.
TTD of Fatigue Score as Measured by EORTC QLQ-C30	2.2 months Interval 1.6 to 2.8	1.4 months Interval 1.1 to 1.9

SECONDARY outcome

Timeframe: Up to 43.4 months

Population: The Safety Population included all participants who received at least 1 dose of study drug.

An AE was defined as any untoward medical occurrence in a subject administered a medicinal product that does not necessarily have a causal relationship with this treatment. TEAEs were defined as any AEs that begin or worsen on or after the start of study drug through 30 days after the last dose of the study drug. The severity was graded based on the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 5.0.

Outcome measures

Outcome measures
Measure	Sacituzumab Govitecan n=268 Participants Participants received sacituzumab govitecan 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met (up to 40.1 months).	Treatment of Physician's Choice (TPC) n=249 Participants Participants received TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent treatment that was determined by the investigator before participant randomization until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met. Dosing per NCCN guidelines (with dose modifications for if toxic) * Eribulin was administered IV at a dose 1.4 mg/m\^2 at North American sites and 1.2 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle (up to 22.5 months). * Capecitabine 1000 to 1250 mg/m\^2 was administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period (up to 12.9 months). * Gemcitabine 800 to 1200 mg/m\^2 was administered IV on Days 1, 8, and 15 of a 28-day cycle (up to 22.3 months). * Vinorelbine 25 mg/m\^2 was administered as a weekly IV injection (up to 8.1 months). Vinorelbine was not allowed as TPC for any participant with Grade 2 neuropathy.
Percentage of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)	100.0 percentage of participants	96.0 percentage of participants

SECONDARY outcome

Timeframe: Up to 43.4 months

Population: Participants in the Safety Population were analyzed.

Treatment-emergent adverse events (TEAEs) were defined as any adverse events (AEs) that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity was graded based on the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 5.0. An AE that met one or more of the following outcomes was classified as serious: * Fatal * Life-threatening * Disabling/incapacitating * Results in hospitalization or prolongs a hospital stay * A congenital abnormality * Other important medical events may also be considered serious AEs if they may require medical or surgical intervention to prevent one of the outcomes listed above

Outcome measures

Outcome measures
Measure	Sacituzumab Govitecan n=268 Participants Participants received sacituzumab govitecan 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met (up to 40.1 months).	Treatment of Physician's Choice (TPC) n=249 Participants Participants received TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent treatment that was determined by the investigator before participant randomization until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met. Dosing per NCCN guidelines (with dose modifications for if toxic) * Eribulin was administered IV at a dose 1.4 mg/m\^2 at North American sites and 1.2 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle (up to 22.5 months). * Capecitabine 1000 to 1250 mg/m\^2 was administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period (up to 12.9 months). * Gemcitabine 800 to 1200 mg/m\^2 was administered IV on Days 1, 8, and 15 of a 28-day cycle (up to 22.3 months). * Vinorelbine 25 mg/m\^2 was administered as a weekly IV injection (up to 8.1 months). Vinorelbine was not allowed as TPC for any participant with Grade 2 neuropathy.
Percentage of Participants Who Experienced Treatment Emergent Serious Adverse Events (TESAEs)	27.6 percentage of participants	19.3 percentage of participants

SECONDARY outcome

Timeframe: Up to 43.4 months

Population: Participants in the Safety Population with post-baseline values were analyzed. 'Number Analyzed' indicates participants with post-baseline values with available data were analyzed.

Blood samples were collected for hematology, serum chemistry, and the laboratory abnormalities were assessed. A treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from baseline at any time postbaseline up to and including the date of last study drug dose plus 30 days.The most severe graded abnormality observed post-baseline for each graded test was counted for each participant. Safety as assessed by grading of laboratory values and AEs according to the National Cancer Institutes' Common Terminology Criteria for Adverse Events (NCI CTCAE) covering grades 0-5 (0=Normal, 1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening, 5=Death). The percentage of participants with worst postbaseline grades 3 or 4 are reported.

Outcome measures

Outcome measures
Measure	Sacituzumab Govitecan n=265 Participants Participants received sacituzumab govitecan 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met (up to 40.1 months).	Treatment of Physician's Choice (TPC) n=242 Participants Participants received TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent treatment that was determined by the investigator before participant randomization until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met. Dosing per NCCN guidelines (with dose modifications for if toxic) * Eribulin was administered IV at a dose 1.4 mg/m\^2 at North American sites and 1.2 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle (up to 22.5 months). * Capecitabine 1000 to 1250 mg/m\^2 was administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period (up to 12.9 months). * Gemcitabine 800 to 1200 mg/m\^2 was administered IV on Days 1, 8, and 15 of a 28-day cycle (up to 22.3 months). * Vinorelbine 25 mg/m\^2 was administered as a weekly IV injection (up to 8.1 months). Vinorelbine was not allowed as TPC for any participant with Grade 2 neuropathy.
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Alanine Aminotransferase Increased	1.1 percentage of participants	2.1 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Hypoalbuminemia	0 percentage of participants	0.4 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Alkaline Phosphatase Increased	0 percentage of participants	0.8 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Aspartate Aminotransferase Increased	1.5 percentage of participants	1.3 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Bilirubin Increased	2.3 percentage of participants	0.8 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Creatinine Increased	0.4 percentage of participants	1.7 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Creatinine Clearance Decreased	2.3 percentage of participants	1.3 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Hypoglycemia	1.1 percentage of participants	0.8 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Hypermagnesemia	0.4 percentage of participants	0 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Hypomagnesemia	0.8 percentage of participants	0 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Hyperkalemia	1.9 percentage of participants	0 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Hypokalemia	4.2 percentage of participants	0.4 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Hyponatremia	0.8 percentage of participants	0.4 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Anemia	7.5 percentage of participants	5.0 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Hemoglobin Increased	1.1 percentage of participants	0 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Leukocytes Decreased	38.9 percentage of participants	25.7 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Leukocytosis	0.4 percentage of participants	0.4 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Lymphocytes Decreased	21.5 percentage of participants	13.7 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Lymphocytes Increased	1.9 percentage of participants	2.1 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Neutrophils Decreased	53.2 percentage of participants	40.2 percentage of participants
Percentage of Participants Who Experienced the Worst Laboratory Abnormalities Grade 3 or 4 Post-Baseline Platelets Decreased	1.9 percentage of participants	3.7 percentage of participants

SECONDARY outcome

Timeframe: Up to 43.4 months

Population: Participants in the Safety Population were analyzed.

ECOG performance status (PS) measured on-therapy assessed participant's performance status on 5 point scale: 0=Fully active/able to carry on all pre-disease performance without restriction;1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature;2=Ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours;3=Capable of only limited self-care;confined to bed or chair more than 50% of waking hours;4=Completely disabled; cannot carry on any self-care; totally confined to bed or chair;5=Dead. Lower score indicated good performance status. Percentage of participants with Baseline ECOG PS score and corresponding changes to the best values post-baseline have been reported.

Outcome measures

Outcome measures
Measure	Sacituzumab Govitecan n=268 Participants Participants received sacituzumab govitecan 10 mg/kg of body weight, administered as a slow IV infusion on Days 1 and 8 of a 21-day treatment cycle until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met (up to 40.1 months).	Treatment of Physician's Choice (TPC) n=249 Participants Participants received TPC (ie, eribulin, capecitabine, gemcitabine, or vinorelbine), administered as a single-agent treatment that was determined by the investigator before participant randomization until progression of disease, occurrence of unacceptable AEs, or another treatment discontinuation criterion was met. Dosing per NCCN guidelines (with dose modifications for if toxic) * Eribulin was administered IV at a dose 1.4 mg/m\^2 at North American sites and 1.2 mg/m\^2 at European sites on Days 1 and 8 of a 21-day cycle (up to 22.5 months). * Capecitabine 1000 to 1250 mg/m\^2 was administered in a 21-day cycle, with capecitabine administered orally twice daily for 2 weeks followed by 1-week rest period (up to 12.9 months). * Gemcitabine 800 to 1200 mg/m\^2 was administered IV on Days 1, 8, and 15 of a 28-day cycle (up to 22.3 months). * Vinorelbine 25 mg/m\^2 was administered as a weekly IV injection (up to 8.1 months). Vinorelbine was not allowed as TPC for any participant with Grade 2 neuropathy.
Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) - Shift From Baseline Value to Best Value During Treatment Baseline ECOG 0, During Treatment ECOG 0	34.9 percentage of participants	38.7 percentage of participants
Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) - Shift From Baseline Value to Best Value During Treatment Baseline ECOG 0, During Treatment ECOG 1	7.8 percentage of participants	8.9 percentage of participants
Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) - Shift From Baseline Value to Best Value During Treatment Baseline ECOG 0, During Treatment ECOG 2	0 percentage of participants	0.4 percentage of participants
Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) - Shift From Baseline Value to Best Value During Treatment Baseline ECOG 1, During Treatment ECOG 0	19.4 percentage of participants	11.5 percentage of participants
Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) - Shift From Baseline Value to Best Value During Treatment Baseline ECOG 1, During Treatment ECOG 1	36.4 percentage of participants	38.3 percentage of participants
Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) - Shift From Baseline Value to Best Value During Treatment Baseline ECOG 1, During Treatment ECOG 2	1.6 percentage of participants	2.1 percentage of participants

Adverse Events

Sacituzumab Govitecan

Serious events: 74 serious events

Other events: 264 other events

Deaths: 234 deaths

Treatment of Physician's Choice (TPC)

Serious events: 48 serious events

Other events: 234 other events

Deaths: 238 deaths

Serious adverse events

Other adverse events

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
Publication restrictions are in place

Restriction type: OTHER