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Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: Results from a single-arm, phase II study in patients with ≥25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy

Dan P. Zandberg, Alain P. Algazi, Antonio Jimeno, James Good, Jérôme Fayette, Nathaniel Bouganim, Neal Ready, Paul Clement, Caroline Even, Raymond Jang,

European Journal of Cancer · 2018 · 267 citations · 15 references

DOI Full text

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TL;DR

Patients with platinum‑refractory recurrent/metastatic head and neck squamous cell carcinoma have poor prognosis, and PD‑1/PD‑L1 are frequently upregulated in this disease. The phase II HAWK study administered durvalumab 10 mg/kg intravenously every two weeks for up to 12 months to immunotherapy‑naïve, PD‑L1‑high (≥25 % tumor cells) patients with platinum‑refractory R/M HNSCC, evaluating objective response, progression‑free survival, and overall survival. Durvalumab achieved a 16.2 % objective response rate (29.4 % in HPV‑positive and 10.9 % in HPV‑negative patients), with median PFS of 2.1 months and OS of 7.1 months; 12‑month PFS and OS were 14.6 % and 33.6 %, respectively, while 57.1 % experienced any‑grade adverse events (8.0 % grade ≥ 3) and 24.1 % remained on treatment or follow‑up, indicating antitumor activity and acceptable safety.

Abstract

BackgroundPatients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) progressing on platinum-based chemotherapy have poor prognoses and limited therapeutic options. Programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) are frequently upregulated in HNSCC. The international, multi-institutional, single-arm, phase II HAWK study (NCT02207530) evaluated durvalumab monotherapy, an anti-PD-L1 monoclonal antibody, in PD-L1-high patients with platinum-refractory R/M HNSCC.Patients and methodsImmunotherapy-naïve patients with confirmed PD-L1-high tumour cell expression (defined as patients with ≥25% of tumour cells expressing PD-L1 [TC ≥ 25%] using the VENTANA PD-L1 [SP263] Assay) received durvalumab 10 mg/kg intravenously every 2 weeks for up to 12 months. The primary end-point was objective response rate; secondary end-points included progression-free survival (PFS) and overall survival (OS).ResultsAmong evaluable patients (n = 111), objective response rate was 16.2% (95% confidence interval [CI], 9.9–24.4); 29.4% (95% CI, 15.1–47.5) for human papillomavirus (HPV)-positive patients and 10.9% (95% CI, 4.5–21.3) for HPV-negative patients. Median PFS and OS for treated patients (n = 112) was 2.1 months (95% CI, 1.9–3.7) and 7.1 months (95% CI, 4.9–9.9); PFS and OS at 12 months were 14.6% (95% CI, 8.5–22.1) and 33.6% (95% CI, 24.8–42.7). Treatment-related adverse events were 57.1% (any grade) and 8.0% (grade ≥3); none led to death. At data cut-off, 24.1% of patients remained on treatment or in follow-up.ConclusionDurvalumab demonstrated antitumour activity with acceptable safety in PD-L1-high patients with R/M HNSCC, supporting its ongoing evaluation in phase III trials in first- and second-line settings. In an ad hoc analysis, HPV-positive patients had a numerically higher response rate and survival than HPV-negative patients.