ESTRO 2025 - Abstract Book

S1733

Clinical - Sarcoma & skin cancer & malignant melanoma

ESTRO 2025

4515

Poster Discussion Efficacy of radioimmunotherapy in locally advanced and metastatic cutaneous squamous cell carcinoma – first results of the combi-RISC study Miriam Mengoni 1,2 , André Glowka 3,4 , Evelyn Gaffal 1 , Thomas Tüting 2 , Andreas D Braun 2 , Daniel Medenwald 3,4 1 Department of Dermatology, University Hospital Schleswig-Holstein, Lübeck, Germany. 2 Department of Dermatology, University Hospital Magdeburg, Magdeburg, Germany. 3 Department of Radiation Oncology, University Hospital Magdeburg, Magdeburg, Germany. 4 Department of Radiation Oncology, Martin Luther University Halle Wittenberg, Halle (Saale), Germany Purpose/Objective: PD-1-based immune checkpoint inhibitors have been approved for the treatment of locally advanced and metastatic cutaneous squamous cell carcinoma (cSCC) in Germany in 2019, and have largely replaced radiochemotherapy as the previous standard-of-care due to their high efficacy. Individual reports have suggested a potential synergistic effect of immune checkpoint inhibitors with radiotherapy (RT), but larger trials analyzing the efficacy of radiotherapy combined with anti-PD-1 inhibitors (aPD-1i) are currently lacking. Material/Methods: We conducted a retrospective analysis of patients with locally advanced and metastatic cSCC who received first-line therapy with aPD-1i (cemiplimab, pembrolizumab) at the University Hospital Magdeburg or the University Hospital Schleswig-Holstein (Campus Lübeck) between September 2018 and August 2024. All patients having received at least two cycles of aPD-1i and clinical or radiological assessments of treatment response were included in this study. Results: We identified 65 patients treated with cSCC between 2018 and 2024, of which 53 patients were included in the final analysis. The median follow-up was 9.73 months (IQR 3.22-16.95). Patients with concurrent RT had an objective response rate (ORR) of 81.3% and a median unmet progression-free survival (mPFS), compared to 75% ORR and 12.52 months mPFS for patients receiving aPD-1i alone. As median radiation doses, a total dose of 55.5 Gy (IQR 36.0-66.0) was administered with a median single dose of 2.3 Gy (IQR 2.0-3.0). Patients receiving concurrent RT showed a higher frequency of adverse events than patients receiving aPD-1i alone (75% vs. 39.3%). These were almost exclusively grade 1-2 CTCAE. In subgroup analyses, no difference was observed between patients receiving greater or less than 50 Gy total radiation dose with concurrent aPD-1i (p=0.97). For patients who completed RT ≥8 weeks prior to initiation of aPD-1i, an ORR of 33.3% with a mPFS of 8.51 months was observed. The median total radiation dose in this cohort was 58 Gy (IQR 54.0-60.0) applied with median single doses of 2 Gy (IQR 2.0-2.0). Conclusion: In our study, we observed a trend towards an improved ORR and mPFS in patients treated with concurrent RT and aPD-1i compared to patients treated with aPD-1i alone or RT prior to aPD-1i. Patients treated with concurrent RT and aPD-1i showed the highest frequency of adverse events, but these were mostly of low severity. These results indicate synergistic effects of RT and aPD-1i. To validate these findings, we are currently expanding our analysis to include a larger number of patients from different treatment centers across Germany and Austria.

Keywords: Cutaneous squamous cell carcinoma, Immunotherapy