Improved Outcomes for Melanoma Brain Metastases With Added Immunotherapy

July 9, 2018

Immune checkpoint inhibitors initiated soon before or after radiosurgery offer excellent outcomes in patients with brain metastases originating from melanoma.

A retrospective analysis found that immune checkpoint inhibitors initiated soon before or after radiosurgery offer excellent outcomes in patients with brain metastases originating from melanoma. Additionally, there was an advantage with regard to several outcomes for anti–programmed death 1 (PD-1) agents compared with anti–cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) agents.

“Importantly, immune checkpoint inhibitors have documented activity in the central nervous system (CNS), and emerging data suggest outcomes after radiosurgery might be improved in patients receiving immune checkpoint inhibitors,” wrote study authors led by Tyler P. Robin, MD, PhD, of the University of Colorado. The researchers reviewed a single institution’s experience with patients who underwent Gamma Knife radiosurgery and who received immune checkpoint inhibitor therapy within 8 weeks before or after the surgery.

The study included a total of 38 patients, 55% of whom were under the age of 70 years. Most patients were male (63%), and most did not have BRAF-mutant melanoma (68%). The majority of patients (63%) had 1 to 3 treated brain metastases, and 58% had a volume of treated brain metastases of < 1 cc. The results of the study were published in the Journal of Neuro-Oncology.

The median follow-up time for all patients was 31.6 months. The 2-year patient-based and lesion-based local control rates were 81% and 92%, respectively. For the full cohort, the median time to out-of-field CNS progression was 8.4 months, and the median time to extra-CNS progression was 7.9 months. The median progression-free survival was 3.4 months, while the median overall survival was not yet reached.

Patients that received anti–PD-1 therapy or combination therapy did not reach the median time to out-of-field CNS progression, compared with 3.1 months with anti–CTLA-4 therapy (P = .049). Similarly, the time to extra-CNS progression was not reached with anti–PD-1 or combination therapy compared with 4.4 months with anti–CTLA-4 therapy (P = .015), and the median progression-free survival was 20.3 months and 2.4 months, respectively (P = .043).

The researchers also compared patients who received the immune checkpoint inhibitor therapy within 7 days of radiosurgery compared with those receiving the drugs outside that window, but no significant differences were seen.

The therapies were generally well tolerated. Three patients had a grade 3 CNS toxicity (radiation necrosis); these toxicities were seen only in those receiving anti–CTLA-4 agents. There were no grade 4 or 5 toxicities.

The authors noted that this was a retrospective single-institution study and is thus limited by the inherent biases in such studies. “Despite these limitations, this study adds to the emerging body of evidence supporting a benefit to immune checkpoint inhibition and radiosurgery for melanoma brain metastases,” they wrote. “Additional studies exploring this paradigm, with a specific emphasis on class of immune checkpoint inhibitor and timing with radiosurgery, are warranted.”