Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/ durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8

J Immunother Cancer. 2020 Oct;8(2):e001378. doi: 10.1136/jitc-2020-001378.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • CD8-Positive T-Lymphocytes
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use*
  • Docetaxel / pharmacology
  • Docetaxel / therapeutic use*
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • Squamous Cell Carcinoma of Head and Neck / drug therapy*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immune Checkpoint Inhibitors
  • Docetaxel
  • durvalumab
  • Cisplatin
  • tremelimumab