Radiation, Immunotherapy Improved Median Overall Survival in Melanoma Brain Metastases

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Researchers hypothesize that radiation may increase the PD-L1 signal on tumors, flagging them for action by blockade inhibitors.
Researchers hypothesize that radiation may increase the PD-L1 signal on tumors, flagging them for action by blockade inhibitors.

Results from a small retrospective study published in the Journal of Neuro-Oncology suggest that there could be a survival benefit to combining radiation with certain checkpoint inhibitors to treat patients with melanoma-related brain metastases.1

Researchers identified 38 patients with melanoma brain metastases who had been treated with Gamma Knife radiosurgery at a single care location between 2012 and 2017 who had also initiated treatment with immune checkpoint inhibitors within 8 weeks of surgery. Across the cohort, median progression-free survival (PFS) after 2 years was 3.4 months and median overall survival (OS) was not reached by that time.

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Three patients experienced hemorrhagic conversion of their brain metastases, which is considered a grade 2 central nervous system toxicity — parameters the researchers deemed “acceptable.”

Within the cohort, patient status was also measured by the type of immune blockade agent that was administered. An anti-PD-1 medication was given to 13 patients, whereas 25 patients received anti-CTLA4 therapies. Patients that were given the anti-PD-1 therapies saw significantly longer PFS times than those who received anti-CTLA1 drugs (20.3 months vs 2.4 months, P = .049).

Considering that only 25% of melanoma patients with brain metastases survive 1 year post-radiosurgery, the fact that median OS was not yet reached at 31.6 months is dramatic, according to researchers.

The study's lead author, Tyler Robin, MD, senior resident in radiation oncology at the University of Colorado, School of Medicine in Aurora, hypothesized that the reason for the benefit was because radiation may increase the PD-L1 signal on tumors, flagging them for action by blockade inhibitors.

“People are actively investigating the combination of immune checkpoint inhibits and radiation, and our data raise the possibility that PD-1 inhibitors are preferential in this setting,” Dr Robin said in a press release.2

References

Robin TP, Breeze RE, Smith DE, et al. Immune checkpoint inhibitors and radiosurgery for newly diagnosed melanoma brain metastases [published online June 16, 2018]. J Neurooncol. doi: 10.1007/s11060-018-2930-5

Sundem G. In melanoma, radiosurgery may combine well with immunotherapy, especially PD-1 inhibitors. Colorado Cancer Blogs website. http://www.coloradocancerblogs.org/in-melanoma-radiosurgery-may-work-well-with-immunotherapy-especially-pd-1-inhibitors/. Published June 22, 2018. Accessed June 26, 2018.

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