A Study Evaluating the Efficacy and Safety of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib + Fulvestrant in Participants With PIK3CA-Mutant, Hormone Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer

PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 or death from any cause (whichever occurs first). Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions was also considered progression. Data for participants without the occurrence of PD or death as of the clinical cutoff date (CCOD) were censored at the time of the last tumor assessment prior to the CCOD. Median PFS was calculated using the Kaplan-Meier methodology.

ORR is defined as the percentage of participants with a complete response (CR) and/or partial response (PR) on at least two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR is defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline.

BOR is defined as the percentage of participants with a CR or PR, as determined by the investigator according to RECIST v1.1. CR is defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline.

DOR is defined as the time from the first occurrence of a CR or PR to the first occurrence of disease progression as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurs first). CR is defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

CBR is defined as the percentage of participants with a CR, PR, and/or stable disease (SD) for at least 24 weeks, as determined by the investigator according to RECIST v1.1. CR= disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline. PD=at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum in the study.

OS is defined as the time from randomization to death from any cause.

TTD in pain is defined as the time from randomization to the first documentation of a ≥ 2-point increase from baseline on the "worst pain" item from the Brief Pain Inventory-Short Form (BPI-SF). BPI-SF is a self-administered questionnaire in which the participant was asked to rate severity on a 10-point scale where 0 represents 'No pain/No interference' and 10 represents 'Pain/Interference as bad as you can imagine'. A ≥2-point change is defined as clinically meaningful difference.

TTD in physical function is defined as the time from randomization to the first documentation of a ≥ 10-point decrease from baseline held for two consecutive cycles or initial decrease followed by death or treatment discontinuation within three weeks of last assessment in the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30) PF scale (items 1-5). A ≥10-point change is defined as a clinically meaningful difference. EORTC QLQ-C30 is a cancer-specific health-related quality-of life (QoL) questionnaire with 30 questions. For the PF scale, participant responses to 5 questions about daily activities (strenuous activities, long walks, short walks, bed/chair rest & needing help with eating, dressing, washing themselves, or using the toilet) is scored on a 4-point scale (1=Not at All to 4=Very Much). Scores are linearly transformed on a scale of 0 to 100, with a high score indicating worst functioning.

TTD in Role Function is defined as the time from randomization to the first documentation of a ≥ 10-point decrease from baseline held for two consecutive cycles, or initial decrease followed by death or treatment discontinuation within three weeks of last assessment in the EORTC QLQ-C30 RF scale (items 6 and 7). A ≥10-point change is defined as clinically meaningful difference. EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. For the role functioning scale, participant responses to the 2 questions "Q6: Were you limited in doing either your work or daily activities" and "Q7: Were you limited in pursuing your hobbies or other leisure time activities" were scored on a 4-point scale (1=Not at All to 4=Very Much). The scores were linearly transformed on a scale of 0 to 100, with a low score indicating better functioning.

TTD in (GHS)/health-related quality of life (HRQoL) is defined as the time from randomization to the first documentation of a ≥ 10-point decrease from baseline held for two consecutive cycles, or initial decrease followed by death or treatment discontinuation within three weeks of last assessment in the EORTC QLQ-30 GHS/HRQoL scale. A ≥10-point change is defined as clinically meaningful difference. EORTC QLQ-C30 is a cancer specific health-related QoL questionnaire. Participant responses to the questions regarding Global Health Status (Q29: GHS; "How would you rate your overall health during the past week?") and Quality of Life (Q30: QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better outcome.

An AE is an untoward medical occurrence in participant administered a pharmaceutical product & regardless of causal relationship with this treatment. An AE can therefore be any unfavorable & unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with use of investigational product, whether or not considered related to investigational product.