Multicenter randomized phase 2 study of nivolumab plus ipilimumab with or without SBRT for advanced Merkel cell carcinoma

Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy associated with Merkel cell polyoma virus or UV exposure. In recent years, anti-PD1/PDL1 therapy has dramatically improved the treatment landscape, but outcome remains poor among patients who progress on this therapy. A multicenter randomized phase 2 study in the United States evaluated addition of stereotactic body radiation therapy (SBRT) to nivolumab plus ipilimumab for unresectable, recurrent or metastatic MCC. The ORR in ICI-naïve patients was 100% (41% complete response) while the ORR in previously ICI treated patients was 31% (15% complete response). Median duration of response was not reached (95% CI 33.9 months-NE) in the ICI-naïve cohort and was 10.8 months (95% CI 4.9 months-NE) in the prior ICI cohort. Treatment was well tolerated. Addition of SBRT was not associated with improvement of response rates. The authors conclude that first-line therapy with nivolumab plus ipilimumab for advanced MCC resulted in exceptionally high ORR of 100%, with durable responses and a manageable safety profile.