Implementation of Double Immune Checkpoint Blockade Increases Response Rate to Induction Chemotherapy in Head and Neck Cancer

Semrau, Sabine

; Gostian, Antoniu-Oreste

; Traxdorf, Maximilian

; Eckstein, Markus ; Rutzner, Sandra ; von der Grün, Jens ; Illmer, Thomas ; Hautmann, Matthias ; Klautke, Gunther ; Laban, Simon

; Brunner, Thomas ; Tamaskovics, Bálint

; Frey, Benjamin

; Zhou, Jian-Guo ; Geppert, Carol-Immanuel ; Hartmann, Arndt ; Balermpas, Panagiotis

; Budach, Wilfried ; Gaipl, Udo

; Iro, Heinrich ; Fietkau, Rainer ; Hecht, Markus

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Simple Summary The study compares the effects on complete remission rate (CR) of a single dose of durvalumab/tremelimumab immediately after a single-cycle platinum and docetaxel as part of induction therapy for a controlled trial in head and neck cancer with chemotherapy alone from a historical collective. The CR rate was 60.3% after induction chemoimmunotherapy (ICIT; induction chemotherapy plus double immune checkpoint blockade) compared with 40.3% after induction chemotherapy (IC) alone. Patients with HPV-positive oropharyngeal cancer may benefit the most from additive double checkpoint inhibition, which is presumably due to the higher amount of infiltrating immune cells. Patients older than 60 years without HPV-positive oropharyngeal cancer are unlikely to benefit. To determine whether a single dose of double immune checkpoint blockade (induction chemoimmunotherapy (ICIT)) adds benefit to induction single-cycle platinum doublet (induction chemotherapy (IC)) in locally advanced head and neck squamous cell carcinoma (HNSCC), patients treated with cisplatin 30 mg/m(2) d1-3 and docetaxel 75 mg/m(2) d1 combined with durvalumab 1500 mg fixed dose d5 and tremelimumab 75 mg fixed dose d5 (ICIT) within the CheckRad-CD8 trial were compared with a retrospective cohort receiving the same chemotherapy (IC) without immunotherapy. The endpoint of this analysis was the complete response rate (CR). A total of 53 patients were treated with ICIT and 104 patients with IC only. CR rates were 60.3% for ICIT and 40.3% for IC (p = 0.018). In the total population (n = 157), the most important predictor to achieve a CR was treatment type (OR: 2.21 for ICIT vs. IC; p = 0.038, multivariate analysis). The most diverse effects in CR rates between ICIT and IC were observed in younger (age <= 60) patients with HPV-positive OPSCCs (82% vs. 33%, p = 0.176), while there was no difference in older patients without HPV-positive OPSCCs (53% vs. 48%). The analysis provides initial evidence that ICIT could result in higher CR rates than IC. Young patients with HPV-positive OPSCCs may have the greatest benefit from additional immune checkpoint inhibitors.

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