Alpelisib Plus Olaparib in Platinum-resistant/Refractory, High-grade Serous Ovarian Cancer, With no Germline BRCA Mutation Detected

Overall survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. If a participant was not known to have died, OS was censored at the latest date the participant was known to be alive (on or before the cut-off date), i.e., the last known date the participant was alive (last contact date).

Overall Response Rate (ORR) was defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR) by blinded independent review committee (BIRC) assessment as per RECIST 1.1 criteria:

• CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm.
• PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Clinical benefit rate (CBR) with confirmed response was defined as the percentage of participants whose best overall response was a confirmed CR or PR, or stable disease (SD) maintained for at least 24 weeks. CR, PR, and SD were determined by BIRC according to RECIST 1.1 criteria.

Time to response (TTR) was defined as the interval from randomization to the first documented occurrence of either complete response (CR) or partial response (PR), which was subsequently confirmed (using the date of initial response, not the confirmation date). CR and PR were determined based on tumor response data assessed by BIRC according to RECIST 1.1 criteria.

Duration of response (DOR) with confirmed response was calculated only for participants whose best overall response was a confirmed complete response (CR) or confirmed partial response (PR), based on tumor response data assessed by BIRC according to RECIST 1.1. The start date was the date of the first documented CR or PR (i.e., the initial response date, not the confirmation date), and the end date was the date of first documented disease progression or death due to underlying cancer. Participants without progression or cancer-related death were censored at the date of their last adequate tumor assessment.

Performance status (PS) was evaluated using the ECOG scale, which comprises six grades (0 to 5), where 0 represents fully active and 5 represents death. Time to definitive deterioration in ECOG PS was defined as the interval from randomization to the date when ECOG PS worsened by at least one category from baseline and remained worsened. Deterioration was considered definitive if there was no subsequent improvement to the baseline category or better. Participants were censored if no definitive deterioration occurred before the earlier of: (i) the analysis cut-off date or (ii) initiation of a new anti-neoplastic therapy. The censoring date was the date of the last PS assessment prior to the cut-off or start of new therapy.

The number of participants with dose reductions/interruptions was assessed and summarized by study treatment.

Dose intensity was computed as the ratio of actual cumulative dose received to actual duration of exposure and summarized by study treatment.

Dose intensity was computed as the ratio of actual cumulative dose received to actual duration of exposure and summarized by study treatment.

Dose intensity was computed as the ratio of actual cumulative dose received to actual duration of exposure and summarized by study treatment.

Venous whole blood samples were collected to characterize the pharmacokinetics of alpelisib when administered in combination with olaparib. AUCtau was listed and summarized using descriptive statistics.

Venous whole blood samples were collected to characterize the pharmacokinetics of alpelisib when administered in combination with olaparib. AUClast was listed and summarized using descriptive statistics.

Venous whole blood samples were collected to characterize the pharmacokinetics of alpelisib when administered in combination with olaparib. Cmax was listed and summarized using descriptive statistics.

Venous blood samples were collected to characterize the pharmacokinetics (PK) of alpelisib when administered in combination with olaparib. Time to maximum observed plasma concentration (Tmax) was calculated using actual sample collection times rather than nominal scheduled sampling times and was summarized using descriptive statistics.

The Functional Assessment of Cancer Therapy-Ovarian (FACT O) is a validated instrument that evaluates quality of life in patients with ovarian cancer. The Trial Outcome Index (TOI) of the FACT-O combines Physical Well Being (PWB), Functional Well Being (FWB), and the Ovarian Cancer Subscale (OCS), and its scores range from 0 to 100, with higher scores indicating better quality of life and physical/functional status. Time to definitive deterioration by 10% in FACT O TOI is defined as the time from randomization to the first occurrence of at least a 10% worsening from baseline with no subsequent improvement above this threshold, or death. Participants without an event before analysis cut off or before starting another anticancer therapy were censored at their last adequate assessment. Time to deterioration was estimated using the Kaplan-Meier method.