Combined immunotherapy with nivolumab and ipilimumab with and without sequential or concomitant stereotactic radiotherapy in patients with melanoma brain metastasis: an international retrospective study
Menée à l'aide de données portant sur 453 patients présentant des métastases cérébrales asymptomatiques ayant pour origine un mélanome (durée médiane de suivi : 29 mois), cette étude analyse l'intérêt, du point de vue de la survie globale, d'ajouter une radiothérapie stéréotaxique concomitante ou séquentielle au traitement standard par ipilimumab et nivolumab (COMBO)
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.
European Journal of Cancer , résumé, 2025