Combined nivolumab and ipilimumab with or without stereotactic body radiation therapy for advanced Merkel cell carcinoma: a randomised, open label, phase 2 trial

The immune stimulating drug combination called ‘ipi-nivo’ (IPIlimumab or Yervoy targets CTLA4 while NIVOlumab or Opdivo targets PD1) has an established role in melanoma, but less is known about using this double therapy in Merkel cell carcinoma. A major study published in the Lancet and led by Kim and co-authors from the Moffitt Cancer Center now addresses this therapy in MCC. Their findings are nicely summarized by Drs. Saiag & Blom in an accompanying editorial. Briefly, the Kim study found that adding radiation did not make ipi-nivo more effective, and, surprisingly, may have even decreased its benefit somewhat. Most importantly, their study establishes ‘ipi-nivo’ as the default approach for patients whose MCC does not respond to a single immune therapy agent such as avelumab or pembrolizumab. Approximately one third of such patients will have benefit from ipi-nivo. Because significant side effects are commonly caused by this combined therapy and there is yet little data about the durability of benefit, routine use of ipi-nivo is currently likely to be focused on patients with ‘refractory’ MCC. Based on the Kim study, ipi-nivo will now likely become the default therapy in patients whose MCC progresses on single-agent immune therapy.