A randomized, open-label, multicenter phase 2 trial showed that both durvalumab plus tremelimumab, and durvalumab monotherapy, had acceptable safety and efficacy in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC; ClinicalTrials.gov Identifier: NCT02319044).1 The phase 2 trial results were published online November 1, 2018, in JAMA Oncology.

The trial enrolled patients with R/M HNSCC between April 15, 2015, and March 16, 2016. Patients were recruited from 127 sites in 15 countries in North America, Europe, and the Asia Pacific region. Eligible patients had PD-L1–­­­­­­­­low or –negative disease. A total of 267 patients were randomly assigned to 1 of 3 treatment arms: durvalumab and tremelimumab (133 individuals), tremelimumab monotherapy (67 individuals), or durvalumab monotherapy (67 individuals).

Objective response rate was 7.8% (95% confidence interval [CI], 3.78-13.79) in the combination arm, 9.2% (95% CI, 3.46%-19.02%) in the durvalumab arm, and 1.6% (95% CI, 0.04%-8.53%) in the tremelimumab arm. No complete responses were reported. Tumor shrinkage was observed in 40 patients (31.0%) in the combination arm, 15 (23.1%) in the durvalumab arm, and 9 (14.3%) in the tremelimumab arm. Median overall survival was 7.6 months for the combination arm, 6 months for the durvalumab arm, and 5.5 months for the tremelimumab arm.

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Incidence of treatment-related adverse events was similar across the treatment arms: 21 patients (15.8%) in the combination arm, 8 (12.3%) in the durvalumab arm, and 11 (16.9%) in the tremelimumab arm experienced these events. Grade 3 or grade 4 treatment-related immune-mediated adverse events, however, occurred only in the combination arm (8 patients). One treatment-related death occurred in the combination arm.

“In patients with R/M HNSCC and low or no PD-L1 tumor cell expression, all 3 regimens exhibited a manageable toxicity profile,” the study authors wrote. “Durvalumab and durvalumab [plus] tremelimumab resulted in clinical benefit, with minimal observed difference between the two. A phase 3 study is under way.”

Disclosure: The original study was sponsored by AstraZeneca. For a full list of disclosures, please refer to the original study.

Reference

  1. Siu LL, Even C, Mesía R, et al. Safety and efficacy of durvalumab with or without tremelimumab in patients with PD-L1-low/negative recurrent or metastatic HNSCC: The phase 2 CONDOR randomized clinical trial [published online November 1, 2018]. JAMA Oncol. doi: 10.1001/jamaoncol.2018.4628