Response and Toxicity Patterns Seen in Patients Treated With Combination Immunotherapy and Radiotherapy in the UNSCARRed (UNresectable Squamous Cell Carcinoma treated With Avelumab and Radical Radiotherapy) Study

Abstract

Combination immunotherapy (IO) with radiotherapy (RT) is theorized to have additive/synergistic effect in treating cancers. PD-1/PD-L1 blockade and RT have both shown very good response rates in cutaneous squamous cell carcinoma (cuSCC) independently. Combination of RT & IO is currently understudy in the UNSCARRed trial. The response/toxicities to RT & IO can be unpredictable, and thus we review here the patterns of response and toxicities seen to date in trial patients.Patients with nonmetastatic unresectable cuSCC were enrolled in UNSCARRed, a single arm study delivering five q2 week cycles of avelumab (PD-L1 inhibitor) with 60-66 Gy / 30-33# RT starting with cycle 2. The patterns of cuSCC response and toxicities experienced by these patients were reviewed as per clinical / imaging studies, pathologic analysis and CTCAE 5.0 criteria, respectively. Biomarker testing including PD-L1 staining is a secondary objective of the trial.7 out of 20 patients have completed the experimental treatment. Median age was 80, and common sites of disease was scalp and head & neck. All except one patient completed the per-protocol treatment, with one patient omitting the last IO cycle due to chest pain. Common toxicities include grade 1-2 dermatitis (all), grade 1 fatigue (3), grade 1 dry mouth (2), and grade 2 cutaneous infections (3). One patient had grade 3 bleeding from tumor site, one had grade 2 hepatitis. All toxicities resolved in follow-up. 6 out of 7 patients experienced an objective response. One patient had progression on treatment with early discontinuation and one experienced biopsy-confirmed pseudoprogression on treatment, but then went on the have a complete response.Patterns of response for RT+IO can be complex compared to RT alone with a potential for progression, pseudoprogression or partial/complete response. Toxicities are limited and easily treated, with patients in this advanced age cohort showing combination of RT+IO appeared feasible with good response. This trial was registered on Clinicaltrials.gov, NCT#:03737721.