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

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.

Time frame: Up to 42.8 months

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

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.

Time frame: Up to 42.8 months

Population: Participants in the ITT Population with available data 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.

Time frame: Up to 42.8 months

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

Time frame: Up to 42.8 months

Population: Participants in the ITT Population with available data 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.

Time frame: Up to 42.8 months

Population: Participants in the ITT Population 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.

Time frame: 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.

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.

Time frame: Up to 43.4 months

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

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

Time frame: 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.

Time frame: Up to 43.4 months

Population: Participants in the Safety 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.

Time frame: Up to 42.8 months

Population: Participants in the ITT Population 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.

Time frame: 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 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).

Time frame: 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 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).

Time frame: Up to 37.8 months

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