Pooled Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone in Patients With Advanced Melanoma

J Clin Oncol. 2025 Mar 10;43(8):938-948. doi: 10.1200/JCO.24.00400. Epub 2024 Nov 6.

Abstract

Purpose: Nivolumab (NIVO) + ipilimumab (IPI) combination and NIVO monotherapy have demonstrated durable clinical benefit in patients with unresectable/metastatic melanoma. This analysis describes long-term overall survival (OS) with the combination or monotherapy pooled across all major company-sponsored trials, as well as clinical factors associated with survival, in patients with immune checkpoint inhibitor (ICI) treatment-naïve unresectable/metastatic melanoma.

Methods: Data were pooled from six CheckMate studies in ICI treatment-naïve patients receiving NIVO + IPI (NIVO 1 mg/kg + IPI 3 mg/kg or NIVO 3 mg/kg + IPI 1 mg/kg) or NIVO monotherapy (3 mg/kg). OS was assessed for each treatment, as well as in select subgroups. Cox proportional multivariate analysis (MVA) and classification and regression tree (CART) analyses were performed within treatment arms.

Results: Median follow-up for OS was 45.0 months for patients treated with NIVO + IPI (n = 839) and 35.8 months for patients treated with NIVO (n = 536). OS was longer with NIVO + IPI versus NIVO monotherapy (hazard ratio, 0.78 [95% CI, 0.67 to 0.91]), with 6-year OS rates of 52% versus 41%, respectively. Consistent benefit was observed in BRAF-mutant and BRAF-wild-type patients and those with normal and elevated lactate dehydrogenase (LDH). Numerical difference in OS was also observed across PD-L1 expression levels, although more pronounced with no/low PD-L1 expression. Clinical factors associated with decreased survival in both the MVA and CART analyses were LDH > upper limit of normal with either treatment, age ≥65 years with NIVO + IPI, and the presence of liver metastases with NIVO monotherapy.

Conclusion: In this large, pooled nonrandomized retrospective analysis, we observed that NIVO + IPI provides longer OS than NIVO in patients with ICI treatment-naïve advanced melanoma and identifies clinical factors that appear to be associated with survival for each treatment, which may assist with treatment decision making.

Trial registration: ClinicalTrials.gov NCT02714218 NCT01721772 NCT01844505 NCT01024231 NCT00730639 NCT01927419.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / administration & dosage
  • Ipilimumab* / administration & dosage
  • Ipilimumab* / adverse effects
  • Ipilimumab* / therapeutic use
  • Male
  • Melanoma* / drug therapy
  • Melanoma* / genetics
  • Melanoma* / mortality
  • Melanoma* / pathology
  • Middle Aged
  • Nivolumab* / administration & dosage
  • Nivolumab* / adverse effects
  • Nivolumab* / therapeutic use
  • Skin Neoplasms* / drug therapy
  • Skin Neoplasms* / mortality
  • Skin Neoplasms* / pathology

Substances

  • Nivolumab
  • Ipilimumab
  • Immune Checkpoint Inhibitors

Associated data

  • ClinicalTrials.gov/NCT02714218
  • ClinicalTrials.gov/NCT01721772
  • ClinicalTrials.gov/NCT01844505
  • ClinicalTrials.gov/NCT01024231
  • ClinicalTrials.gov/NCT00730639
  • ClinicalTrials.gov/NCT01927419