Safety and efficacy of nivolumab in challenging subgroups with advanced melanoma who progressed on or after ipilimumab treatment: A single-arm, open-label, phase II study (CheckMate 172)

Eur J Cancer. 2019 Nov:121:144-153. doi: 10.1016/j.ejca.2019.08.014. Epub 2019 Sep 30.

Abstract

Background: Limited data are available on nivolumab in challenging subgroups with advanced melanoma. We report outcomes of nivolumab after prior ipilimumab in patients who are typically excluded from clinical trials.

Patients and methods: In this phase II, single-arm, open-label, multicentre study (CheckMate 172), patients with advanced melanoma who progressed on or after ipilimumab received nivolumab 3 mg/kg, every 2 weeks for up to 2 years. The primary objective was incidence of grade ≥3, treatment-related select adverse events (AEs).

Results: At a minimum follow-up of 18 months, grade ≥3 treatment-related select AEs with the most variation across subgroups were diarrhoea and colitis (1.1% [n = 11] and 0.3% [n = 3] for the total population [n = 1008]; 0.6% [n = 1] and 0.6% [n = 1] for patients with an asymptomatic central nervous system [CNS] metastasis [n = 165; 16.4%]; 4.5% [n = 3] and 3.0% [n = 2] for patients with an Eastern Cooperative Oncology Group performance status [ECOG PS] of 2 [n = 66; 6.5%]; 2.4% [n = 2] and 0% for those who experienced a grade 3/4 immune-related AE [irAE] with prior ipilimumab [n = 84; 8.3%]; and 0% and 0% for autoimmune disease [n = 25; 2.5%], respectively). Median overall survival was 21.4 months in the total population and was 11.6, 2.4, 21.5, and 18.6 months in patients with a CNS metastasis, ECOG PS 2, a grade 3/4 irAE with prior ipilimumab, and autoimmune disease, respectively.

Conclusions: In this large, phase II clinical trial of patients with advanced melanoma who progressed on or after ipilimumab, nivolumab demonstrated a safety profile consistent with that of prior clinical trials. ClinicalTrials.gov ID: NCT02156804.

Keywords: Advanced melanoma; Autoimmune; CNS metastasis; ECOG performance status; Ipilimumab; Nivolumab.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Disease Progression
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Follow-Up Studies
  • Humans
  • Ipilimumab / therapeutic use*
  • Male
  • Melanoma / drug therapy*
  • Melanoma / mortality
  • Melanoma / pathology
  • Middle Aged
  • Neoplasm Staging
  • Nivolumab / therapeutic use*
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Ipilimumab
  • Nivolumab

Associated data

  • ClinicalTrials.gov/NCT02156804