BACKGROUND: CheckMate 649 (NCT02872116) is a randomized, open-label phase 3 study as first-line (1L) therapy for patients (pts) with GC/GEJC/EAC. Primary results showed statistically significant improvement in overall survival (OS) and progression-free survival (PFS)for N+C versus C in pts whose tumors expressed programmed death-ligand 1 (PD-L1) combined positive score (CPS) ≥ 5. Prior analyses for 24-month follow-up (FUP) showed pts with CPS ≥ 5 generally maintained HRQOL and lower deterioration risk with N+C compared with C alone. Here we report additional exploratory analyses with 36-month FUP data for pts with CPS ≥ 5.
METHODS: Functional Assessment of Cancer Therapy–Gastric Cancer (FACT-Ga) and EQ-5D-3L (EQ-5D) were performed at baseline and every 6 weeks during treatment. Longitudinal change from baseline (CFB) in EQ-5D Visual Analog Scale (VAS), Utility Index (UI), FACT-Ga total score, and subscales were analyzed using a mixed model for repeated measures. FACT-G GP5 (“I am bothered by side effects of treatment.”) item responses were analyzed descriptively. Time to first symptom deterioration (TTSD), time until definitive deterioration (TuDD), and time to improvement (TTI) were estimated using Kaplan-Meier estimators and stratified Cox models; deterioration/improvement was based on prespecified meaningful change thresholds.
RESULTS: In total, 1581 pts were randomized to N+C and C; of these, 955 had CPS ≥ 5, including 822 pts with both baseline and postbaseline PROs (N+C, n = 422; C, n = 400). Least-squares mean differences favored N+C at most time points for EQ-5D, FACT-Ga total, Gastric Cancer Subscale (GaCS), and Physical Well-Being (PWB) scores and were comparable for other FACT subscale scores (data not shown). GP5 responses initially increased for pts postbaseline in both treatment groups then decreased over time for N+C while pts treated with C remained relatively stable (data not shown). TTI slightly favored N+C with the majority of HR >1, but none were significantly different between treatments (data not shown). TTSD favored N+C with all HR <1 and significant decreased risk of deterioration, with HR and 95% confidence interval (CI) < 1 in EQ-5D UI (0.80, 0.65-0.99), FACT-Ga total score (0.75, 0.58-0.97), and GaCS subscale (0.65, 0.50-0.83). TuDD showed statistically significant delays in deterioration with HR and 95% CI < 1 for all scale scores: PWB (0.71, 0.55-0.91), Social Well-Being (0.70, 0.53-0.92), Emotional Well-Being (0.67, 0.49-0.92), Functional Well-Being (0.60, 0.46-0.78), FACT-G total score (0.64, 0.49-0.84), GaCS subscale (0.61, 0.45-0.84), FACT-Ga total (0.60, 0.43-0.83), EQ-5D UI (0.67, 0.52-0.86; UK value set), and EQ-5D VAS (0.71, 0.55-0.91).
CONCLUSIONS: The 36-month FUP results confirm the earlier 24-month FUP findings that pts generally maintained HRQOL with N+C compared with C alone. CFB in EQ-5D, FACT-Ga total, GaCS, and PWB favored N+C at most time points. Pts treated with N+C were no more bothered by side effects than pts treated with C alone. N+C decreased deterioration risk compared with C along with the improvement of OS and PFS, suggesting favorable benefits in 1L therapy for pts with CPS ≥ 5.
