Association of health-related quality of life (HRQoL) and treatment safety with nivolumab (NIVO) in patients (pts) with resected stage IIIB/C or IV melanoma: Analysis of CheckMate 238 four-year follow-up (FU) data.
Authors: Weber Jeffrey S. , Gogas Helen , Sun Xiaowu , Yip Christine , Taylor Fiona , Braverman Julia , Lobo Maurice , Thakkar Pratik K. , Moshyk Andriy , Larkin James , Ascierto Paolo Antonio 
Published: June 2021

9574 Background: In CheckMate 238, NIVO 3 mg/kg vs ipilimumab 10 mg/kg showed significantly longer recurrence-free survival and a lower rate of grade 3–4 treatment-related adverse events (TRAEs) in pts with completely resected stage IIIB/C or IV melanoma. This analysis assessed the association of long-term HRQoL and TRAEs in NIVO-treated pts in this trial. Methods: HRQoL was assessed using EORTC QLQ-C30 (global health status [GHS] and physical/emotional functioning) and EQ-5D-3L visual analogue scale (VAS) questionnaires administered after randomization, during 1 y of treatment (wk 5, 7, 11, 17, 25, 37, and 49), at posttreatment FU visits 1 and 2 (FU1 and FU2; 30 and 114 days after last dose), and at survival FU visits up to 4 y after last dose (EQ-5D-3L only). NIVO-treated pts were grouped based on whether they had experienced a grade 3–4 TRAE, any-grade TRAE leading to NIVO discontinuation, or any-grade select (immune-related) TRAE on treatment or up to 100 days after last dose. Longitudinal change from baseline (BL) in scores was assessed for pts with and without TRAEs having patient-reported outcome data at BL and ≥1 post-BL assessment (HRQoL population) using descriptive statistics. QLQ-C30 subscale and VAS changes of 10 and 7, respectively, were considered clinically meaningful. Results: The HRQoL population comprised 446 of 453 pts randomized to NIVO. EQ-5D-3L assessments were completed by 81% of survivors (263/324) after 4 y post-randomization. Grade 3–4 TRAEs occurred in 17% of NIVO-treated pts (77/446). A slight trend toward deterioration of GHS from BL on treatment was noted, with clinically meaningful deterioration at posttreatment FU1 (mean [SD], −13.8 [25.0]) and FU2 (−10.3 [22.0]; last available time point). For the VAS, a similar trend on treatment was noted (−6.9 [28.3] at wk 11), with a clinically meaningful deterioration after NIVO discontinuation (−9.9 [27.0] at FU1) and a return to BL level by the start of survival FU. For pts without grade 3–4 TRAEs, mean change from BL scores remained stable (ie, no clinically meaningful deterioration on treatment or during FU). Any-grade TRAEs led to NIVO discontinuation in 9% of pts (42/446); HRQoL findings were similar to those for pts with grade 3–4 TRAEs. The most common any-grade TRAE was fatigue (35%). No clinically meaningful deterioration in VAS was noted for any select TRAE during FU except for hyperthyroidism (8%), with which deterioration occurred at FU1. EORTC QLQ-C30 physical and emotional functioning results will be presented. Conclusions: In CheckMate 238, pts with TRAEs showed early HRQoL deterioration after NIVO discontinuation, but HRQoL returned to BL levels with no sustained deterioration during survival FU. Overall, HRQoL was maintained on treatment and over a long-term FU period in pts with resected melanoma receiving adjuvant NIVO. Clinical trial information: NCT02388906.