First-line therapy of advanced head and neck cancer with double checkpoint blockade and radioimmunotherapy - first results.

Introduction The aim of this study is to evaluate the feasibility, safety and effectiveness of radioimmunotherapy with double checkpoint inhibition after induction immunochemotherapy in advanced head and neck cancer. Patients and methods: In this open phase II study, patients with stage III - IVB received an induction cycle of combined chemo-immunotherapy with cisplatin / docetaxel plus durvalumab / tremelimumab followed by radioimmunotherapy. An increase in CD8 cells in tumor and peritumoral tissue served as a selection criterion for radioimmunotherapy and was determined on biopsies before and after chemo-induction therapy. Results: A total of 56 patients have been treated with an initial median intratumoral density of 342 CD8 + cells / mm2. Induction treatment led to a pathological complete response (pCR) in the rebiopsy in 27 patients (48 % ) and to a relevant increase in CD8 + cells (3 fold median increase) in additional 25 patients (45 % ). Grade 3-4 adverse reactions occurred in 38 patients (68 % ) and consisted mainly of leukopenia (43 % ) and infections (29 % ). Six patients (11 % ) developed a grade 3-4 immunologically-related adverse event. The univariate analysis calculated the p16 positivity, the PD-L1 expression on immune cells and the intratumoral CD8 + cell density as predictors for a pCR. In the multivariable analysis, only the intratumoral CD8 + cell density emerged as an independent predictor for a pCR (OR 1.0012 per cell / mm², 95 %  CI 10001 to 1.0022, p = 0.016). Conclusion: Induction chemotherapy with cisplatin / docetaxel and durvalumab / tremelimumab in patients with advanced head and neck cancer can be applied safely and leads to a distinct immune response combined with a high rate of remission.

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