Details

Autor(en) / Beteiligte

• Segal, Neil H.
• Ou, Sai-Hong I.
• Balmanoukian, Ani
• Fury, Matthew G.
• Massarelli, Erminia
• Brahmer, Julie R.
• Weiss, Jared
• Schöffski, Patrick
• Antonia, Scott J.
• Massard, Christophe
• Zandberg, Dan P.
• Khleif, Samir N.
• Xiao, Feng
• Rebelatto, Marlon C.
• Steele, Keith E.
• Robbins, Paul B.
• Angra, Natasha
• Song, Xuyang
• Abdullah, Shaad
• Butler, Marcus

Titel

Safety and efficacy of durvalumab in patients with head and neck squamous cell carcinoma: results from a phase I/II expansion cohort

Ist Teil von

• European journal of cancer (1990), 2019-03, Vol.109, p.154-161

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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%). 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. clinicaltrials.gov NCT01693562; MedImmune study 1108. •Durvalumab monotherapy was safe in previously treated recurrent/metastatic head and neck squamous cell carcinoma.•Durable antitumour responses were observed, similar to other tumour cohorts.•Objective response rate and disease control rate were greater in patients with ≥25% vs <25% tumoural PD-L1 expression.