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

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.