Efficacy and safety of nivolumab + relatlimab (NIVO+RELA) versus nivolumab + ipilimuab (NIVO+IPI) in the first-line (1L) treatment of advanced melanoma: updated data from an indirect treatment comparison.

Schadendorf D, Tawbi HA, Lipson EJ, Hodi S, Ascierto PA, Larkin J, Lao CD, Grob JJ, Ejzykowicz F, Palaia J, Garcia-Horton V, Zhou ZY, Christensen D, Rosenblatt L, McDonald L, Ratto B, Salvatore A, Patel D, Sakkal LA, Dalle S, Long G. Annals of Dermatology and Venereology – FMC, 4, no. 8, Supplement 1, (Dec 01 2024): A82-A83, doi:https://doi.org/10.1016/j.fander.2024.09.510.

Abstract

Introduction

An indirect comparison between NIVO  +  RELA and NIVO  +  IPI, 2 approved immunotherapy combination treatment options for patients with advanced melanoma, was previously conducted using individual patient data from the pivotal RELATIVITY-047 (RELA-047; NIVO  +  RELA vs. NIVO) and CheckMate 067 (CM-067; NIVO  +  IPI or NIVO vs. IPI) clinical trials. Here, we present the results obtained from the updated 3-year data from the RELA-047 trial.

Materials and methods

Inverse probability of treatment weighting was used to adjust for imbalances between patient baseline characteristics across the 2 trials. Database freezes were selected to best align follow-up duration in RELA-047 (median 34 months) and CM-067 (median 38 months). Investigator-rated progression-free survival (PFS), investigator-rated confirmed objective response rates (ORR), overall survival (OS), melanoma-specific survival (MSS), treatment-related adverse events (TRAEs), and TRAEs leading to treatment discontinuation were analyzed. PFS, OS, and ORR were assessed in key subgroups. PFS, OS, and MSS were compared using Kaplan-Meier curves and Hazard Ratios (HRs); ORRs were compared using Odds Ratios (ORs). The weighted NIVO arm of each trial was compared for methodology validation.

Results

After weighting, key baseline characteristics were balanced between NIVO  +  RELA ( n  =  339) and NIVO  +  IPI ( n  =  297). Efficacy results after weighting were similar between NIVO  +  RELA and NIVO  +  IPI, as well as between NIVO arms. Similar results between NIVO arms validate the methodology used. Across subgroups, efficacy appeared similar between treatments, although trends favoring NIVO  +  IPI were observed for ORR in patients with BRAF-mutated disease or LDH  >  2  ×  ULN. TRAEs were less frequent with NIVO  +  RELA (23%) compared with NIVO  +  IPI (61%); all-grade TRAEs leading to treatment discontinuation occurred in 17% and 41% of patients, respectively.

Discussion

Consistent with previous results, these updated treatment comparison data suggest that treatment of 1L with NIVO  +  RELA may have comparable efficacy to NIVO  +  IPI, with less toxicity, in patients with advanced melanoma. The results should be interpreted with caution due to differences in study design and changes in the treatment landscape. Research is ongoing to determine which patients respond best to each combination.

Conclusion

Consistent with previous results, these updated treatment comparison data suggest that 1L treatment with NIVO  +  RELA may have comparable efficacy to NIVO  +  IPI, while exhibiting less toxicity, in patients with advanced melanoma.