Data collection and statistical analysis
CDMS
EVENT
The planned sample size for the study was 240 (~120 patients in each arm), providing 85% power to show that ORR for dostarlimab plus chemotherapy is not more than 15% worse than pembrolizumab plus chemotherapy at the 10% one-sided level of significance, assuming the true ORR was 45% for both treatment groups. ‘Similarity’ was implied as the ORR for dostarlimab plus chemotherapy not being >15% lower than the ORR for pembrolizumab plus chemotherapy.Efficacy analyses (stratified by PD-L1 and smoking status) were performed using the intent-to-treat (ITT) population, defined as all patients randomized to study treatment. Safety analyses were performed using the safety population, defined as all patients randomized to study treatment who received at least one dose of study medication.Data were collected using Veeva EDC (CDMS) versions 20R3, 21R1, 21R3, 22R1, 22R2 and 22R3 and analyzed using SAS software version 9.4. Baseline demographics and characteristics for the ITT population are presented using descriptive statistics and safety outcomes (AEs) are presented by frequency and proportion. For the primary endpoint (ORR by BICR), the Mantel and Haenszel method with Sato’s variance estimator was used for treatment comparison (stratified by PD-L1 status and smoking status); the difference in ORR between groups and its 80% CI are reported. The Clopper–Pearson method was used to calculate point estimates for ORR, with 95% CIs. ORR in patients with PD-L1 TPS ≥ 1% was included as a prespecified subgroup analysis, in addition to the PD-L1 stratification subgroups TPS < 1%, 1–49%, and ≥50%.PFS and OS were analyzed using Kaplan–Meier methodology. PFS and OS HRs and 95% CIs were estimated using a Cox proportional hazards model with PD-L1 status and smoking status as stratification factors. Maturity for time-to-event analyses was calculated as a percentage of patients in the ITT population (PFS and OS) or as a percentage of the subset of patients with CR or PR (duration of response) that had experienced an event at data cut-off. Duration of follow-up was calculated using the Kaplan–Meier estimate of potential follow-up