Adding avelumab to standard chemoradiotherapy did not improve progression-free survival (PFS) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), according to trial results published in The Lancet Oncology.

The double-blind, phase 3 JAVELIN Head and Neck 100 trial ( Identifier: NCT02952586) randomly assigned 697 patients with treatment-naive, HNSCC to receive avelumab or placebo in addition to chemoradiotherapy. The chemoradiotherapy consisted of cisplatin plus intensity-modulated radiotherapy with 70 Gy of standard fractionation.

At baseline, the patients’ median age was 60 years, and 83% were men. Most (65%) were White, 27% were Asian, 3% were Black or African American, and 5% were another race.

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Human papillomavirus was present in 35% of patients, and the nodal stage was N0 to N2b in 53%. The primary tumor site was the oropharynx for most patients, followed by the hypopharynx, the larynx, and the oral cavity.

The median follow-up was 14.6 months in the avelumab arm and 14.8 months in the placebo arm. The objective response rate was similar between the groups, at 74% in the avelumab arm and 75% in the placebo arm.

The median PFS was not reached in either treatment group, but the hazard ratio (HR) favored placebo at 1.21 (95% CI, 0.93-1.57; P =.92). Most HRs favored placebo in subgroup analyses. However, avelumab appeared to provide a PFS benefit in patients with high programmed cell death 1 ligand 1 (PD-L1) tumor expression at baseline (HR, 0.59; 95% CI, 0.28-1.22; P =.03).

Treatment-related grade 3 and higher adverse events occurred in 80% of patients in the avelumab group and 74% of those in the placebo group. The most common events were neutropenia, mucosal inflammation, dysphagia, and anemia.

The study authors concluded that adding avelumab to chemoradiotherapy did not improve overall outcomes in patients with high-risk locally advanced HNSCC. However, the potential PFS benefit among patients with high PD-L1 expression may warrant further study.

Disclosure: This research was supported by Pfizer and Merck kGaA. Study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Lee NY, Ferris RL, Psyrri A, et al. Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2021;22:450-462. doi:10.1016/S1470-2045(20)30737-3