CheckMate 459: Health-related quality of life (HRQoL) in a randomized, multicenter phase III study of nivolumab (NIVO) versus sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC).

Abstract

483 Background: SOR is approved as 1L therapy for pts with aHCC, but there is still an unmet need to help improve or maintain HRQoL. This phase 3 study compared HRQoL of NIVO vs SOR as 1L therapy in pts with aHCC as an exploratory endpoint. Methods: FACT-Hep was administered cycle 1, day 1 and every other cycle. The effect of NIVO vs SOR on HRQoL using FACT-Hep was assessed via repeated measures mixed models (MMRM). Kaplan–Meier curves and Cox proportional-hazards models determined between-treatment differences in time to first and time until definitive deterioration (TTD/TUDD) based on prespecified thresholds for minimally important differences. The GP5 item from FACT-Hep was used to assess the burden associated with treatment side effects. Results: 743 pts with aHCC were randomized to NIVO (n = 371) or SOR (n = 372). Median OS was 16.4 mo for NIVO, 14.7 mo for SOR (HR 0.85 [95% CI 0.72–1.02]; P = 0.0752). ORR was 15% for NIVO, 7% for SOR (OR 2.41 [95% CI 1.48–3.92]). HRQoL scores were completed at baseline by 94.6% and 92.5% of participants, respectively, and were similar (FACT-Hep total: NIVO 140.7 [SD 21.5] and SOR 140. 6 [SD 19.1]. Questionnaire compliance rates exceeded 70% at most visits. MMRM analyses yielded clinically meaningful and statistically significant least squares means differences favoring NIVO on FACT-Hep total (10.1 [95% CI 7.3–13.0]), physical well-being (PWB; 2.0 [95% CI 1.4–2.6]), and functional well-being (FWB; 2.5 [95% CI 1.7–3.2]) scores. No sub-scales favored sorafenib. TTD was significantly delayed in NIVO for FACT-Hep total (HR 0.62 [95% CI 0.51–0.74]), PWB (HR 0.62 [95% CI 0.52–0.74]), FWB (HR 0.73 [95% CI 0.61–0.88]), and hepatobiliary cancer subscale (HR 0.57 [95% CI 0.48–0.69]). TUDD results were consistent with TTD. A greater proportion of NIVO pts did not experience increased burden of side effects (50%–67.7%) compared with SOR (26.8%–45%) based on the GP5 item. Conclusions: These patient-reported findings demonstrate that pts taking NIVO had superior HRQoL and reduced side effect burden, further supporting clinical data showing a treatment benefit for 1L NIVO in aHCC. Clinical trial information: NCT02576509.