Health-related quality of life (HRQoL) with pembrolizumab (pembro) in resected high-risk stage II melanoma in the phase 3 KEYNOTE-716 study.

9581 Background: Adjuvant pembro improved RFS vs placebo (HR, 0.61; 95% CI, 0.45-0.82) and had manageable safety in patients (pts) with resected high-risk stage II melanoma at second interim analysis of KEYNOTE-716 (NCT03553836). HRQoL results are presented. Methods: Pts aged ≥12 y with resected stage IIB/C melanoma were randomized 1:1 to adjuvant pembro 200 mg (2 mg/kg for pts ≥12 and < 18 y) Q3W or placebo for ≤17 cycles. Change from baseline in HRQoL was an exploratory end point. EORTC QLQ-C30 and EQ-5D-5L were administered at baseline; cycles 5, 9, 13, and 17 in y 1; every 12 wk in y 2; and every 6 mo in y 3. The HRQoL population included all pts who received ≥1 dose of study treatment and had ≥1 HRQoL assessment available. Least-squares mean (LSM) change from baseline to wk 48 in EORTC QLQ-C30 global health status (GHS)/quality of life (QoL) and physical functioning (PF) and EQ-5D-5L visual analog scale (VAS) were calculated using a constrained longitudinal data analysis model; HRQoL score was the response variable with treatment by time interaction and T stage at baseline as covariates. Empirical mean change from baseline in QLQ-C30 GHS/QoL and PF scores over time was evaluated. A ≥10-point improvement or decline in QLQ-C30 scores was considered clinically meaningful. Data cutoff was June 21, 2021. Results: Of 976 pts enrolled, 969 were included in the HRQoL population (483 pembro; 486 placebo). Median follow-up in the ITT population was 20.5 mo (range, 4.6-32.7). At wk 48, compliance (adherence) for EORTC QLQ-C30 was 83.4% for pembro and 89.3% for placebo and completion was 70.6% and 75.7%, respectively. At wk 48, compliance for EQ-5D-5L was 84.1% for pembro and 90.0% for placebo and completion was 71.2% and 76.3%, respectively. QLQ-C30 GHS/QoL and PF and EQ-5D-5L VAS scores were similar between arms at baseline. LSM change from baseline to wk 48 in QLQ-C30 GHS/QoL score was −4.49 (95% CI, −6.19 to −2.79) for pembro and −0.82 (95% CI, −2.47 to 0.83) for placebo (LSM difference: −3.67; 95% CI, −5.91 to −1.44). LSM change from baseline to wk 48 in QLQ-C30 PF score was −3.27 (95% CI, −4.61 to −1.92) for pembro and −1.77 (95% CI, −3.07 to −0.46) for placebo (LSM difference: −1.50; 95% CI, −3.33 to 0.32). LSM change from baseline to wk 48 in EQ-5D-5L VAS score was −2.19 (95% CI, −3.52 to −0.85) for pembro and −0.25 (95% CI, −1.54 to 1.04) for placebo (LSM difference: −1.94; 95% CI, −3.72 to −0.16). LSM change from baseline to wk 48 in other QLQ-C30 functioning and symptom scales was similar in both arms. Empirical mean change from baseline in QLQ-C30 GHS/QoL and PF was similar over 96 wk in both arms. Conclusions: No clinically meaningful decreases in EORTC QLQ-C30 or EQ-5D-5L VAS scores were observed for adjuvant pembro or placebo. These results, along with improved RFS and manageable safety, support the use of adjuvant pembro in resected high-risk stage II melanoma. Clinical trial information: NCT03553836.