Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
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, JG; Frey, B; Donaubauer, AJ; Becker, I; Semrau, S; Hartmann, A; Balermpas, P; Budach, W; Gaipl, US; Iro, H; Gostian, AO; Fietkau, R.
Induction chemoimmunotherapy followed by CD8+ immune cell-based patient selection for chemotherapy-free radioimmunotherapy in locally advanced head and neck cancer.
J Immunother Cancer. 2022; 10(1):
Doi: 10.1136/jitc-2021-003747
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- Co-Autor*innen der Med Uni Graz
- Brunner Thomas Baptist
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- 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).
- Find related publications in this database (using NLM MeSH Indexing)
- Aged - administration & dosage
- Antineoplastic Combined Chemotherapy Protocols - adverse effects, therapeutic use
- Biomarkers, Tumor - administration & dosage
- CD8-Positive T-Lymphocytes - immunology
- Female - administration & dosage
- Head and Neck Neoplasms - immunology, mortality, therapy
- Humans - administration & dosage
- Immune Checkpoint Inhibitors - therapeutic use
- Induction Chemotherapy - administration & dosage
- Male - administration & dosage
- Middle Aged - administration & dosage
- Patient Selection - administration & dosage
- Radioimmunotherapy - adverse effects, methods
- Squamous Cell Carcinoma of Head and Neck - immunology, mortality, therapy
- Find related publications in this database (Keywords)
- radioimmunotherapy