Safety and efficacy of durvalumab in patients with head and neck squamous cell carcinoma: Results from a phase I/II expansion cohort Journal Article
| Authors: | Segal, N. H.; Ou, S. H. I.; Balmanoukian, A.; Fury, M. G.; Massarelli, E.; Brahmer, J. R.; Weiss, J.; Schöffski, P.; Antonia, S. J.; Massard, C.; Zandberg, D. P.; Khleif, S. N.; Xiao, F.; Rebelatto, M. C.; Steele, K. E.; Robbins, P. B.; Angra, N.; Song, X.; Abdullah, S.; Butler, M. |
| Article Title: | Safety and efficacy of durvalumab in patients with head and neck squamous cell carcinoma: Results from a phase I/II expansion cohort |
| Abstract: | Introduction: Durvalumab selectively blocks programmed cell death ligand-1 (PD-L1) binding to programmed cell death-1. Encouraging clinical activity and manageable safety were reported in urothelial carcinoma, non–small-cell lung cancer (NSCLC), hepatocellular carcinoma (HC) and small-cell lung cancer (SCLC) in a multicenter phase I/II study. Safety and clinical activity in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) were evaluated in the expansion phase. Methods: Patients received 10 mg/kg of durvalumab intravenously every 2 weeks for 12 months or until confirmed progressive disease or unacceptable toxicity. The primary objective was safety; clinical activity was a secondary objective. Results: Sixty-two patients were enrolled and evaluable (received first dose ≥24 weeks before data cutoff). Median age was 57 years; 40.3% were human papillomavirus (HPV)-positive; 32.3% had tumour cell PD-L1 expression ≥25%, and 62.9% were current/former smokers. They had a median of 2 prior systemic treatments (range, 1–13). All-causality adverse events (AEs) occurred in 98.4%; drug-related AEs occurred in 59.7% and were grade III–IV in 9.7%. There were no drug-related discontinuations or deaths. Objective response rate (blinded independent central review) was 6.5% (15.0% for PD-L1 ≥25%, 2.6% for <25%). Median time to response was 2.7 months (range, 1.2–5.5); median duration was 12.4 months (range, 3.5–20.5+). Median progression-free survival was 1.4 months; median overall survival (OS) was 8.4 months. OS rate was 62% at 6 months and 38% at 12 months (42% for PD-L1 ≥25%, 36% for <25%). Conclusions: Durvalumab safety in HNSCC was manageable and consistent with other cohorts of the study. Early, durable responses in these heavily pretreated patients warrant further investigation; phase III monotherapy and combination therapy studies are ongoing. Clinical trial registry: clinicaltrials.gov NCT01693562; MedImmune study 1108. © 2019 Elsevier Ltd |
| Keywords: | immunotherapy; head and neck squamous cell carcinoma; human papillomavirus; pd-l1; checkpoint inhibition |
| Journal Title: | European Journal of Cancer |
| Volume: | 109 |
| ISSN: | 0959-8049 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2019-03-01 |
| Start Page: | 154 |
| End Page: | 161 |
| Language: | English |
| DOI: | 10.1016/j.ejca.2018.12.029 |
| PROVIDER: | scopus |
| PUBMED: | 30731276 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2019 -- Source: Scopus |
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