Induction chemoimmunotherapy followed by CD8+ immune cell-based patient selection for chemotherapy-free radioimmunotherapy in locally advanced head and neck cancer

Hecht M, Eckstein M, Rutzner S, von der Grün J, Illmer T, Klautke G, Laban S, Hautmann MG, Brunner TB, Tamaskovics B, Hinke A, Zhou J, Frey B, Donaubauer AJ, Becker I, Semrau S, Hartmann A, Balermpas P, Budach W, Gaipl U, Iro H, Fietkau R, Gostian AO (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 10

Article Number: e003747

Journal Issue: 1

DOI: 10.1136/jitc-2021-003747

Abstract

Purpose The first aim of the trial is to study feasibility of combined programmed death protein ligand 1/cytotoxic T-lymphocyte-associated protein 4 inhibition concomitant to radiotherapy. In addition, efficacy of the entire treatment scheme consisting of induction chemoimmunotherapy followed by chemotherapy-free radioimmunotherapy (RIT) after intratumoral CD8 +immune cell-based patient selection will be analyzed. Methods Patients with stage III-IVB head and neck squamous cell carcinoma were eligible for this multicenter phase II trial. Treatment consisted of a single cycle of cisplatin 30 mg/m² days 1-3, docetaxel 75 mg/m² day 1, durvalumab 1500 mg fix dose day 5 and tremelimumab 75 mg fix dose day 5. Patients with increased intratumoral CD8 +immune cell density or pathological complete response (pCR) in the rebiopsy entered RIT up to a total dose of 70 Gy. Patients received further three cycles of durvalumab/tremelimumab followed by eight cycles of durvalumab mono (every 4 weeks). The intended treatment for patients not meeting these criteria was standard radiochemotherapy outside the trial. Primary endpoint was a feasibility rate of patients entering RIT to receive treatment until at least cycle 6 of immunotherapy of ≥80%. Results Between September 2018 and May 2020, 80 patients were enrolled (one excluded). Out of these, 23 patients had human papilloma virus (HPV)-positive oropharyngeal cancer. Median follow-up was 17.2 months. After induction chemoimmunotherapy 41 patients had pCR and 31 had increased intratumoral CD8 +immune cells. Of 60 patients entering RIT (primary endpoint cohort), 10 experienced imiting toxic (mainly hepatitis) and four discontinued for other reasons, resulting in a feasibility rate of 82%. The RIT cohort (n=60) had a progression-free survival (PFS) rate at one and 2 years of 78% and 72%, respectively, and an overall survival rate at one and 2 years of 90% and 84%, respectively. Patients with HPV-positive oropharyngeal cancers had greater benefit from RIT with a 2-year PFS rate of 94% compared with 64% for HPV-negative oropharyngeal cancers and other locations. In the entire study cohort (n=79) the 2-year PFS rate was 68% (91% for HPV-positive oropharynx vs 59% for others). Toxicity grade 3-4 mainly consisted of dysphagia (53%), leukopenia (52%) and infections (32%). Conclusions The trial met the primary endpoint feasibility of RIT. Induction chemo-immunotherapy followed by chemotherapy-free RIT after intratumoral CD8 +immune cell-based patient selection has promising PFS. Trial registration number The trial was registered with ClinicalTrials.gov (identifier: NCT03426657). The trial was conducted as investigator-sponsored trial (IST).

Authors with CRIS profile

Involved external institutions

Klinikum Chemnitz Germany (DE) Otto-von-Guericke-Universität Magdeburg Germany (DE) Goethe-Universität Frankfurt am Main Germany (DE) Universität Ulm Germany (DE) Universität Regensburg Germany (DE) Heinrich-Heine-Universität Düsseldorf Germany (DE)

How to cite

APA:

Hecht, M., Eckstein, M., Rutzner, S., von der Grün, J., Illmer, T., Klautke, G.,... Gostian, A.-O. (2022). Induction chemoimmunotherapy followed by CD8+ immune cell-based patient selection for chemotherapy-free radioimmunotherapy in locally advanced head and neck cancer. Journal for ImmunoTherapy of Cancer, 10(1). https://doi.org/10.1136/jitc-2021-003747

MLA:

Hecht, Markus, et al. "Induction chemoimmunotherapy followed by CD8+ immune cell-based patient selection for chemotherapy-free radioimmunotherapy in locally advanced head and neck cancer." Journal for ImmunoTherapy of Cancer 10.1 (2022).

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