Combined immunotherapy with nivolumab and ipilimumab with and without sequential or concomitant stereotactic radiotherapy in patients with melanoma brain metastasis: An international retrospective study

Eur J Cancer. 2025 Jul 25:225:115567. doi: 10.1016/j.ejca.2025.115567. Epub 2025 Jun 9.

Abstract

Background: Ipilimumab plus nivolumab (COMBO) is the standard treatment in patients with asymptomatic melanoma brain metastases (MBM). We report a retrospective study aiming to assess the outcome of patients with MBM treated with COMBO with or without sequential/concomitant stereotactic radiotherapy (SRT).

Methods: MBM patients treated with COMBO with or without SRT have been retrieved: demographics, steroid treatment, Central Nervous System [CNS]-related symptoms, BRAF status, radiotherapy (yes/no and timing) or surgery, number of MBM, maximum diameter of metastasis, overall response rate (ORR), progression-free (PFS) and overall survival (OS) have been analyzed.

Results: 453 patients were included: 190 received COMBO alone, 107 received COMBO and concomitant SRT, 156 COMBO and sequential SRT, respectively. At multivariable analysis the line of treatment [> 1st vs 1st: HR 2.60 (1.93-3.50)], sequential SRT vs no radiotherapy [HR 0.45 (0.32-0.64)], concomitant SRT vs no radiotherapy [HR 0.48 (0.33-0.69)], steroids [HR 1.56 (1.17-2.08)], age [HR 1.01 (1.00-1.02)] and number of MBM [≥ 3 vs 1 HR 1.55 (1.11-2.17)), 2 vs 1 HR 1.53 (1.02-2.31)] at baseline were associated with OS. There was no significant difference between patients who received concomitant vs sequential SRT. At a median follow-up of 29 months, the median-OS in the overall population was 17.8 months while in those who received SRT was 27.3 (15.3-39.4) for patients receiving sequential radiotherapy and 22.2 (12.7-31.7) for those receiving radiotherapy concomitantly to COMBO. The incidence of radionecrosis was 10.3 %. Toxicities were consistent with previous studies.

Conclusions: Our results suggest a better OS in patients who receive SRT plus COMBO, regardless of timing of SRT. Prospective studies are needed to validate our findings.

Keywords: Comboimmunotherapy; Concomitant radiotherapy; Melanoma brain metastases; Sequential radiotherapy.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Brain Neoplasms* / mortality
  • Brain Neoplasms* / secondary
  • Brain Neoplasms* / therapy
  • Female
  • Humans
  • Immunotherapy* / methods
  • Ipilimumab* / administration & dosage
  • Ipilimumab* / adverse effects
  • Ipilimumab* / therapeutic use
  • Male
  • Melanoma* / mortality
  • Melanoma* / pathology
  • Melanoma* / secondary
  • Melanoma* / therapy
  • Middle Aged
  • Nivolumab* / administration & dosage
  • Nivolumab* / adverse effects
  • Nivolumab* / therapeutic use
  • Radiosurgery* / adverse effects
  • Radiosurgery* / methods
  • Radiosurgery* / mortality
  • Retrospective Studies

Substances

  • Ipilimumab
  • Nivolumab