Faculty Collaboration Database

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. Eur J Cancer 2019 Jan;107:142-152

Date

12/24/2018

Pubmed ID

30576970

DOI

10.1016/j.ejca.2018.11.015

Scopus ID

2-s2.0-85058541688 (requires institutional sign-in at Scopus site)   187 Citations

Abstract

BACKGROUND: 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.

PATIENTS AND METHODS: 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).

RESULTS: 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.

CONCLUSION: 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.

Author List

Zandberg DP, Algazi AP, Jimeno A, Good JS, Fayette J, Bouganim N, Ready NE, Clement PM, Even C, Jang RW, Wong S, Keilholz U, Gilbert J, Fenton M, Braña I, Henry S, Remenar E, Papai Z, Siu LL, Jarkowski A, Armstrong JM, Asubonteng K, Fan J, Melillo G, Mesía R

Author

Stuart J. Wong MD Center Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
B7-H1 Antigen
Biomarkers, Tumor
Female
Follow-Up Studies
Head and Neck Neoplasms
Humans
International Agencies
Lymphatic Metastasis
Male
Middle Aged
Neoplasm Recurrence, Local
Prognosis
Salvage Therapy
Survival Rate
Young Adult