Nivolumab, Stereotactic Radiation May Improve Survival in Melanoma Brain Metastases

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The PD-1‒targeting drug nivolumab (Opdivo) combined with stereotactic radiation may work synergistically and help improve overall survival (OS) while resulting in minimal neurotoxicity in brain metastatic melanoma patients, according to a new study published on December 27, 2015, in the Annals of Oncology.

Investigators at Moffitt Cancer Center in Tampa, Fla., looked and this combination approach and found it was well-tolerated and OS appeared to be prolonged compared to standard current treatment.

The team retrospectively analyzed data from 26 patients who were treated with nivolumab and stereotactic radiotherapy in two separate Moffitt clinical trials. The researchers discovered that the combination of nivolumab and stereotactic radiation therapy was safe in patients with both resected and unresected brain metastases. Of the 26 metastatic melanoma patients, only one patient experienced treatment-related headaches and no other neurologic toxicities. No scalp reactions were reported either.

In these 26 patients, 73 brain metastases were treated over 30 sessions and radiation was administered before, during, and after nivolumab. The researchers found there were eight local brain metastases failures (11%) with a ≥20% increase in volume. In these eight cases, hemorrhage was noted in four cases and edema in seven cases. Patients with unresected metastatic disease had a median OS of 11.8 months from the start of radiation therapy and 12 months from the start of nivolumab treatment. This was an improvement from historical levels of survival for melanoma patients with brain metastases who on average survive 8 to 10 months after surgery or radiation alone. 

“This study shows the two treatments can be combined safely and may work synergistically in the treatment of melanoma brain metastases. This study is a step forward as we work towards improving outcomes for patients with brain metastases,” said study author Kamran Ahmed, MD, who is a resident in Department of Radiation Oncology at Moffitt Cancer Center, in a press release.

Dr. Ahmed noted that these findings warrant further evaluation in prospective trials. Greater awareness in the treatment for this patient population is occurring now because of former President Jimmy Carter and his recent metastatic melanoma diagnosis. Carter was successfully treated with focused stereotactic radiation to the brain and anti-PD-1 therapy.

Nivolumab binds to and blocks the activation of PD-1, an immunoglobulin superfamily transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), which is overexpressed on certain cancer cells. Nivolumab has been approved by the US Food and Drug Administration to treat advanced non-small cell lung cancer, renal cell carcinoma, and melanoma.  However, the impact of nivolumab on brain metastases has been unclear.