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

• Published in: European journal of cancer (1990) 2019-01, Vol.107, p.142-152
• Main Authors: Zandberg, Dan P., Algazi, Alain P., Jimeno, Antonio, Good, James S., Fayette, Jérôme, Bouganim, Nathaniel, Ready, Neal E., Clement, Paul M., Even, Caroline, Jang, Raymond W., Wong, Stuart, Keilholz, Ulrich, Gilbert, Jill, Fenton, Moon, Braña, Irene, Henry, Stephanie, Remenar, Eva, Papai, Zsuzsanna, Siu, Lillian L., Jarkowski, Anthony, Armstrong, Jon M., Asubonteng, Kobby, Fan, Jean, Melillo, Giovanni, Mesía, Ricard
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies; Antibodies, Monoclonal - therapeutic use; Antineoplastic Agents, Immunological - therapeutic use; B7-H1 Antigen - metabolism; Biomarkers, Tumor - metabolism; Female; Follow-Up Studies; Head and neck cancer; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; HPV; Humans; Immunotherapy; International Agencies; Lymphatic Metastasis; Male; Middle Aged; Monoclonal; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - metabolism; Neoplasm Recurrence, Local - pathology; Prognosis; Recurrent or metastatic; Salvage Therapy; Squamous Cell Carcinoma of Head and Neck - drug therapy; Squamous Cell Carcinoma of Head and Neck - metabolism; Squamous Cell Carcinoma of Head and Neck - secondary; Survival Rate; Young Adult
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2018.11.015

Patients 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. Immunotherapy-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). Among 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. Durvalumab 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. •This study assessed durvalumab in patients with R/M HNSCC and PD-L1-high expression.•Patients had failed 1 platinum-based chemotherapeutic regimen in the R/M setting.•The ORR for all patients was 16.2% with a median OS of 7.1 months.•HPV-positive patients had a numerically higher response rate and longer survival.•Durvalumab showed antitumour activity with acceptable safety in the HAWK study.