Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/ durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8
Markus Hecht, Antoniu Oreste Gostian, Markus Eckstein, Sandra Rutzner, Jens von der Grün, Thomas Illmer, Matthias G Hautmann, Gunther Klautke, Simon Laban, Thomas Brunner, Axel Hinke, Ina Becker, Benjamin Frey, Sabine Semrau, Carol I Geppert, Arndt Hartmann, Panagiotis Balermpas, Wilfried Budach, Udo S Gaipl, Heinrich Iro, Rainer Fietkau, Markus Hecht, Antoniu Oreste Gostian, Markus Eckstein, Sandra Rutzner, Jens von der Grün, Thomas Illmer, Matthias G Hautmann, Gunther Klautke, Simon Laban, Thomas Brunner, Axel Hinke, Ina Becker, Benjamin Frey, Sabine Semrau, Carol I Geppert, Arndt Hartmann, Panagiotis Balermpas, Wilfried Budach, Udo S Gaipl, Heinrich Iro, Rainer Fietkau
Abstract
Background: To determine safety and efficacy of single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab in stage III-IVB head and neck cancer.
Methods: Patients received a single cycle of cisplatin 30 mg/m² on days 1-3 and docetaxel 75 mg/m² on day 1 combined with durvalumab 1500 mg fix dose on day 5 and tremelimumab 75 mg fix dose on day 5. Patients with pathologic complete response (pCR) in the rebiopsy after induction treatment or at least 20% increase of intratumoral CD8+ cell density in the rebiopsy compared with baseline entered radioimmunotherapy with concomitant durvalumab/tremelimumab. The objective of this interim analysis was to analyze safety and efficacy of the chemoimmunotherapy-induction treatment before radioimmunotherapy.
Results: A total of 57 patients were enrolled, 56 were treated. Median pretreatment intratumoral CD8+ cell density was 342 cells/mm². After induction treatment, 27 patients (48%) had a pCR in the rebiopsy and further 25 patients (45%) had a relevant increase of intratumoral CD8+ cells (median increase by a factor of 3.0). Adverse event (AE) grade 3-4 appeared in 38 patients (68%) and mainly consisted of leukopenia (43%) and infections (29%). Six patients (11%) developed grade 3-4 immune-related AE. Univariate analysis computed p16 positivity, programmed death ligand 1 immune cell area and intratumoral CD8+ cell density as predictors of pCR. On multivariable analysis, intratumoral CD8+ cell density predicted pCR independently (OR 1.0012 per cell/mm², 95% CI 1.0001 to 1.0022, p=0.016). In peripheral blood CD8+ cells, the coexpression of programmed death protein 1 significantly increased especially in patients with pCR.
Conclusions: Single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab is feasible and achieves a high biopsy-proven pCR rate.
Keywords: CD8-Positive T-lymphocytes; Phase II as topic; clinical trials; combined modality therapy; head and neck neoplasms; radioimmunotherapy.
Conflict of interest statement
Competing interests: MH conflict of interest with Merck Serono (advisory role, speakers’ bureau, honoraria, travel expenses, research funding); MSD (advisory role, speakers’ bureau, travel expenses, research funding); AstraZeneca (research funding); Novartis (research funding); BMS (advisory role, honoraria, speakers’ bureau); Teva (travel expenses). ME conflict of interest with Diaceutics (employment, honoraria, advisory role, speakers’ bureau, travel expenses); AstraZeneca (honoraria, advisory role, speakers’ bureau, travel expenses); Roche (honoraria, travel expenses); MSD (honoraria, speakers’ bureau); GenomicHealth (honoraria, advisory role, speakers bureau, travel expenses); Astellas (honoraria, speakers’ bureau); Janssen-Cilag (honoraria, advisory role, research funding, travel expenses); Stratifyer (research funding, patents). SR conflict of interest with AstraZeneca (research funding); MSD (research funding). MGH conflict of interest with Roche (stock); Varian (stock); Sanofi (stock); AstraZeneca (honoraria); BMS (honoraria, advisory role); MSD (honoraria, advisory role); Merck Serono (honoraria); Celgene (honoraria). GK conflict of interest with BMS (advisory role); Lilly (advisory role); Roche (advisory role). SL conflict of interest with AstraZeneca (honoraria, advisory role); BMS (honoraria, advisory role, speakers’ bureau); MSD (honoraria, advisory role); Merck Serono (honoraria, speakers’ bureau); ISA-Pharmaceuticals (research funding). A Hinke conflict of interest with Roche (honoraria). SS conflict of interest with Strycker (stock); Varian (stock); Abbot (stock); Crispr Techn. (stock); Pfizer (stock); Merck Serono (stock); Symrise (stock); Ortho (honoraria, advisory role, speakers’ bureau, research funding, travel expenses); PharmaMar (speakers’ bureau, travel expenses); Haema (speakers’ bureau). A Hartmann conflict of interest with BMS (honoraria, advisory role); MSD (honoraria, advisory role); Roche (honoraria, advisory role, research funding); AstraZeneca (honoraria, advisory role, research funding); Boehringer Ingelheim (honoraria); Abbvie (honoraria); Cepheid (advisory role, research funding); Quiagen (advisory role); Janssen-Cilag (honoraria, advisory role, research funding); Ipsen (honoraria, advisory role); NanoString Technologies (advisory role, research funding, expert testimony); Illumina (advisory role); 3DHistech (advisory role); Diaceutics (advisory role); BioNTech (research funding). WB conflict of interest with BMS (advisory role); MSD (advisory role); Merck Serono (advisory role); Pfitzer (advisory role); AstraZeneca (advisory role). USG conflict of interest with AstraZeneca (advisory role, research funding); BMS (advisory role); MSD (research funding); Sennewald Medizintechnik (travel expenses). RF conflict of interest with MSD (honoraria, advisory role, research funding, travel expenses); Fresenius (honoraria); BrainLab (honoraria); AstraZeneca (honoraria, advisory role, research funding, travel expenses); Merck Serono (advisory role, research funding, travel expenses); Novocure (advisory role, speakers’ bureau, research funding); Sennewald (speakers’ bureau, travel expenses).
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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