Undergoing immunotherapy within a month of stereotactic radiosurgery (SRS) for the treatment of melanoma brain metastases resulted in an improved response to treatment compared with undergoing the two treatments with a longer amount of time between them, according to the results of a study published in Cancer.
Patients in the study who underwent the two therapies within 4 weeks of each other had a significantly greater median percent reduction in lesion volume regardless of whether SRS occurred before or after immunotherapy.
“The mechanism by which concurrent immunotherapy increases the effect of radiation remains unknown, and it is unclear whether this effect is isolated to melanoma or perhaps could be applied to other cancer types that also develop brain metastases,” wrote researcher Veronica L. S. Chiang, MD, of the Department of Neurosurgery at Yale School of Medicine in New Haven, Connecticut, and colleagues. “Further testing and validation of these results in larger prospective studies and in other cancer types are warranted.”
According to the authors, it remains unknown whether combining the systemic use of immune checkpoint inhibitors with standard local treatment modalities might alter efficacy or toxicity of the drugs. In this study, Chiang and colleagues looked at 75 melanoma patients who had a combined 566 brain metastases treated with both SRS and immune checkpoint therapy between 2007 and 2015. Treatments were considered to have occurred concurrently if treatment was given within 4 weeks of each other (n = 33). The researchers then compared lesion volume change at 1.5, 3, and 6 months after treatment.
Patients included in the study underwent either anti–CTLA-4 treatment (72%) or anti–PD-1 treatment (28%). Median lesion size was 105.6 mm3.
Patients who underwent concurrent treatment had significantly greater median percent reduction in lesion volume compared with non-concurrent treatment at all time points: 1.5 months (–63.1% vs –43.2%, P < .0001), 3 months (–83% vs –52.8%, P < .0001), and 6 months (–94.9% vs –66.2%, P < .0001). The difference between concurrent and non-concurrent treatment remained significant even when the researchers looked only at 20 patients who had undergone both concurrent and non-concurrent treatment.
“Although our study was not designed to look at survival, a subanalysis of our data also suggests a trend toward increased survival with concurrent treatment, although this did not reach statistical significance,” the researchers wrote.
In addition, Chiang and colleagues found a significantly greater median percent reduction in lesion volume among those patients who underwent anti–PD-1 treatment compared with anti–CTLA-4 treatment at 1.5 months (–71.1% vs –48.2%, P < .0001), 3 months (–89.3% vs –66.2%, P < .0001), and 6 months (–95.1% vs –75.9%, P = .0004).
“Our study results suggest that 1) immunotherapy can have a synergistic effect with radiosurgery in the treatment of brain metastases, even in those not known to have programmed death ligand 1 expression, and 2) the early lesional response is greater and more rapid with concurrent administration of immunotherapy and SRS,” the researchers concluded.