Real-world comparison of survival with nivolumab (NIVO) + relatlimab (RELA) vs NIVO + ipilimumab (IPI) in advanced melanoma.

Abstract

9527 Background: An indirect-treatment (Tx)-comparison (ITC) suggested first-line (1L) NIVO + RELA may have similar efficacy vs NIVO + IPI in clinical trial patients (pts) with untreated advanced melanoma. However, there is no real-world study comparing these Tx. This study compared survival outcomes among pts with advanced melanoma treated with 1L NIVO + RELA or NIVO + IPI in the Flatiron Health EHR-derived de-identified database, which includes ≥ 280 oncology clinics across the US. Methods: Data were extracted for pts aged ≥ 18 yrs who received 1L NIVO + RELA or NIVO + IPI between March 18, 2022 (date of NIVO + RELA FDA approval) and March 31, 2024. Pts who received adjuvant Tx, including anti–PD-1, were included, while pts with other primary cancers or treated in any clinical trial were excluded. Endpoints were OS and real-world PFS from start of 1L Tx. Outcomes were summarized using Kaplan–Meier methods, and Tx were compared using Cox models adjusted for age, sex, practice type, BRAF, brain metastases (mets), liver mets, prior adjuvant anti–PD-1 monotherapy, time from advanced melanoma diagnosis to start of 1L Tx, ECOG PS, stage, and LDH. Missing data for ECOG PS, BRAF, stage, and LDH were imputed. Results: Median (m) follow-up was 7.4 mo for NIVO + RELA (N = 408) and 7.7 mo for NIVO + IPI (N = 600). The NIVO + RELA group was older (m [IQR], 74.1 [65.9–81.5] yrs) than the NIVO + IPI group (66.2 [57.3–74.5] yrs), but generally had better prognostic factors (Table). Prior anti–PD-1 adjuvant Tx was 12% in both groups, while time from end of adjuvant Tx to 1L Tx and time from advanced melanoma diagnosis to 1L Tx trended longer with NIVO + RELA vs NIVO + IPI (Table). 74% of the NIVO + RELA group and 70% of the NIVO + IPI group were missing PD-L1 status, while 16% vs 20%, respectively, had PD-L1 > 1% (P = 0.61). mOS was not reached (NR) for both groups, with 95% CIs of 20.1–NR mo for NIVO + RELA vs 21.5–NR mo for NIVO + IPI (adjusted HR, 0.91 [95% CI, 0.70–1.18]). Median rwPFS was longer with NIVO + RELA (11.5 [8.9–18.7] mo) vs NIVO + IPI (4.8 [3.7–6.3] mo; adjusted HR, 0.75 [0.61–0.91]). Conclusions: This real-world study supports the ITC observation that NIVO + RELA and NIVO + IPI convey similar OS benefits for pts with advanced melanoma. The longer rwPFS for NIVO + RELA vs NIVO + IPI warrants additional research with longer follow-up and further evaluation of baseline characteristics, as the NIVO + IPI group had poorer prognostic factors. Important limitations included short follow-up, covariate missingness, and potential unmeasured confounding. NIVO + RELA(N = 408) NIVO + IPI(N = 600) Community practice, a % 62 77 Brain mets, a % 9 21 Liver mets, a % 7 11 LDH ≤ ULN, a,b % 76 61 BRAF mutant, a,b % 40 50 ECOG PS, b %0–1≥ 2 8911 8911 Time from advanced diagnosis to 1L Tx (mo) a , m (IQR) 1.4 (0.8–3.0) 1.1 (0.7–2.1) Time from end of adjuvant therapy to 1L Tx (mo), m (IQR) 13.0 (3.4–30.0) 8.3 (0.1–20.3) a Between-Tx difference P < 0.05. b Includes imputed values.