Long-Term Survival in Patients With Advanced Melanoma

JAMA Netw Open. 2024 Aug 1;7(8):e2426641. doi: 10.1001/jamanetworkopen.2024.26641.

Abstract

Importance: Long-term survival data from clinical trials show that survival curves of patients with advanced melanoma treated with immune checkpoint inhibitors (ICIs) gradually reach a plateau, suggesting that patients have a chance of achieving long-term survival.

Objective: To investigate long-term survival in patients with advanced melanoma treated with ICIs outside clinical trials.

Design, setting, and participants: Cohort study using prospectively collected data from the nationwide Dutch Melanoma Treatment Registry, including patients in the Netherlands with advanced melanoma treated with first-line ICIs from 2012 to 2019. Data were analyzed from January to September 2023.

Exposures: Patients were treated with first-line ipilimumab-nivolumab, antibodies that target programmed cell death (anti-PD-1), or ipilimumab.

Main outcomes and measures: Progression-free survival (PFS) and melanoma-specific survival were analyzed, and a Cox proportional hazards model was used to investigate factors associated with PFS after reaching partial response (PR) or complete response (CR).

Results: A total of 2490 patients treated with first-line ICIs were included (median [IQR] age, 65.0 [55.3-73.0] years; 1561 male patients [62.7%]). Most patients had an Eastern Cooperative Oncology Group Performance Status of 1 or lower (2202 patients [88.5%]) and normal lactate dehydrogenase levels (1715 patients [68.9%]). PFS for all patients was 23.4% (95% CI, 21.7%-25.2%) after 3 years and 19.7% (95% CI, 18.0%-21.4%) after 5 years. Overall survival for all patients was 44.0% (95% CI, 42.1%-46.1%) after 3 years and 35.9% (95% CI, 33.9%-38.0%) after 5 years. Patients with metastases in 3 or more organ sites had a significantly higher hazard of progression after reaching PR or CR (adjusted hazard ratio, 1.37; 95% CI, 1.11-1.69).

Conclusions and relevance: This cohort study of patients with advanced melanoma treated with ICIs in clinical practice showed that their survival reached a plateau, comparable with patients participating in clinical trials. These findings can be used in daily clinical practice to guide long-term surveillance strategies and inform both physicians and patients regarding long-term treatment outcomes.

MeSH terms

  • Aged
  • Cohort Studies
  • Female
  • Humans
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Ipilimumab / therapeutic use
  • Male
  • Melanoma* / drug therapy
  • Melanoma* / mortality
  • Middle Aged
  • Netherlands / epidemiology
  • Nivolumab / therapeutic use
  • Progression-Free Survival
  • Prospective Studies
  • Registries
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology

Substances

  • Immune Checkpoint Inhibitors
  • Ipilimumab
  • Nivolumab