Durvalumab With or Without Tremelimumab in Recurrent or Metastatic HNSCC With Low/No PD-L1 Expression


Key Points

  • Responses were observed in 7.8% of the combination group and 9.2% of the durvalumab group.
  • Disease control rates at 6 months were 13.2% and 21.5%.

In a randomized phase II trial reported in JAMA Oncology, Siu et al found that the combination of the programmed cell death ligand 1 (PD-L1) inhibitor durvalumab (Imfinzi) plus the cytotoxic T-lymphocyte–associated protein 4 (CTLA-4) inhibitor tremelimumab and durvalumab alone showed evidence of activity in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with low/no PD-L1 expression.    

Study Details

In the open-label trial, 267 patients with disease progression after 1 platinum-containing regimen in the recurrent or metastatic setting  from 127 sites in North America, Europe, and Asia Pacific were randomly assigned 2:1:1 between April 2015 and March 2016 to receive durvalumab 20 mg/kg every 4 weeks  plus tremelimumab 1 mg/kg every 4 weeks for 4 cycles followed by durvalumab 10 mg/kg every 2 weeks (n = 133); durvalumab alone at 10 mg/kg every 2 weeks (n = 67); or tremelimumab alone at 10 mg/kg every 4 weeks for 7 doses then every 12 weeks for 2 doses (n = 67). Low/no PD-L1 expression was defined as tumor cell expression ≤ 25%.

Response Rates

Median follow-up was 6.5 months in the combination arm, 6.0 months in the durvalumab group, and 5.2 months in the tremelimumab group. Objective response rates were 7.8% (10 patients with partial response) in the combination group, 9.2% (6 with partial response) in the durvalumab group, and 1.6% (1 with partial response) in the  tremelimumab group. Disease control rates at 6 months were 13.2%, 21.5%, and 1.6%. Median duration of response was 9.4 months in the combination group and not evaluable in the other groups. Responses were ongoing in 5, 4, and 1 patient at data cutoff. Median overall survival was 7.6, 6.0, and 5.5 months.

Adverse Events

Grade 3 or 4 treatment-related adverse events occurred in 15.8% of the combination group, 12.3% of the durvalumab group, and 16.9% of the tremelimumab. Treatment-related immune-mediated adverse events of any grade occurred in 19.5%, 7.7%, and 0% of patients. Grade 3 or 4 treatment-related immune-mediated adverse events were observed only in the combination group (6.0%).

The investigators concluded, “In patients with [recurrent or metastatic] HNSCC and low or no PD-L1 tumor cell expression, all 3 regimens exhibited a manageable toxicity profile. Durvalumab and durvalumab + tremelimumab resulted in clinical benefit, with minimal observed difference between the two. A phase III study is under way.”

The study was sponsored by AstraZeneca.

Lillian L. Siu, MD, FRCPC, of the Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, is the corresponding author for the JAMA Oncology article.

Disclosure: See study authors’ full disclosures at

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