Durvalumab for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): Preliminary results from a single-arm, phase 2 study

Abstract

Purpose: R/M HNSCC patients (pts) who have progressed on platinum- based chemotherapy have a poor prognosis and limited therapeutic options. Programmed cell death 1 (PD-1) and its ligand PD-L1 are frequently up-regulated in several tumor types, including HNSCC. The global, single-arm, Phase 2 HAWK study evaluated anti-PD-L1 immunotherapy durvalumab as monotherapy in PD-L1 high pts with R/M HNSCC who have failed platinum-based chemotherapy. Methods: Immunotherapy-naive pts aged ≥18 years with confirmed PDL1 high expression (≥25% of tumor cells, Ventana SP263 assay) who had progression or recurrence during/after 1 platinum-based regimen for R/M HNSCC received durvalumab 10 mg/kg IV every 2 weeks up to 12 months or until progression, starting another anticancer therapy, consent withdrawal, or unacceptable toxicity. Primary endpoint was objective response rate (ORR; blinded independent central review, RECIST v1.1); secondary endpoints included progression-free survival (PFS) and overall survival (OS). Results: As of Sept 26, 2016, 112 pts from 12 countries had received treatment (median age 60 years, 71.4% male, 34.7% human papillomavirus [HPV]+, and 61.6% current/former smokers). Median durations of treatment and follow-up were 3.45 and 5.96 months. Among evaluable pts (n = 111), ORR was 13.5% (95% CI 7.8-21.3) overall and 26.5% (95% CI 12.9-44.4) and 7.9% (95% CI 2.6-17.6) for HPV+ and HPV- pts; among responders (n = 15), 12 (80%) had ongoing response at data cutoff (DCO). 35 pts (31.5%) had stable disease ≥8 weeks. Median PFS was 2.3 months (95% CI 1.9-3.7); 34 pts (30.4%) were alive at DCO (OS data immature). The incidence of grade ≥3 treatment-related adverse events (AEs) was 9.8%. No treatment-related AE led to death. 88 pts (78.6%) discontinued study treatment, 65 (58%) due to progressive disease, 10 (8.9%) due to all-causality AEs. Conclusions: Durvalumab demonstrated promising antitumor activity with acceptable safety profile in PD-L1 high R/M HNSCC pts, supporting its potential use, and the opportunity to improve efficacy, in combination therapy.