Still abscoping it out.

Top Line: Does radiation produce an abscopal effect with combination immunotherapy for Merkel cell carcinoma?

The Study: Single agent immunotherapy (ICI) is the current standard treatment for advanced MCC. In this randomized phase 2 trial, 50 patients (48% ICI-naive) with advanced MCC were randomized to receive combination nivolumab and ipilimumab with or without “subablative” SBRT (24Gy in 3 fractions) to at least 1 tumor site. Patients had to have at least two sites of measurable disease, and at least one site of disease had to be left untreated by SBRT. SBRT was delivered during week 2 of systemic therapy. There was no significant difference in overall response rate (ORR) between ipi+nivo alone (72%) and ipi+nivo+SBRT (52%). ICI-naive patients had the greatest response with a 100% ORR that included 41% with complete responses. Among those with prior ICI, the ORR was 31% with 15% having complete response. Most responses were durable, but progression after response was much more common in those with prior ICI treatment (50% v 9%). Obviously, abscopal SBRT trials aren’t the same as trials where SBRT is delivered to all sites of disease to prolong response. A takeaway from this trial was that no irradiated lesions recurred after SBRT. While this trial shows that subablative SBRT doesn’t produce an abscopal response to combination immunotherapy, it doesn’t address the potential benefit of SBRT to all sites of oligometastatic disease. Furthermore, SBRT did not increase toxicity during ICI treatment.

TBL: Patients with ICI-naive, advanced MCC have excellent responses to combination immunotherapy, but SBRT does not further enhance response through an abscopal effect. | Kim, Lancet 2022