Neil H Segal1, Sai-Hong I Ou2, Ani Balmanoukian3, Matthew G Fury4, Erminia Massarelli5, Julie R Brahmer6, Jared Weiss7, Patrick Schöffski8, Scott J Antonia9, Christophe Massard10, Dan P Zandberg11, Samir N Khleif12, Feng Xiao13, Marlon C Rebelatto14, Keith E Steele14, Paul B Robbins14, Natasha Angra15, Xuyang Song14, Shaad Abdullah15, Marcus Butler16. 1. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA. Electronic address: segaln@mskcc.org. 2. Chao Family Comprehensive Cancer Center, Department of Medicine, Division of Hematology/Oncology, University of California School of Medicine, Orange, CA, USA. 3. Hematology/Oncology, The Angeles Clinic and Research Institute, Los Angeles, CA, USA. 4. Department of Medicine, Head and Neck Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 5. Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 6. Thoracic Oncology Program, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA. 7. Division of Hematology/Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA. 8. Department of Oncology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium. 9. Department of Thoracic Oncology, Moffitt Cancer Center, Tampa, FL, USA. 10. Université Paris Saclay, Université Paris-Sud, Drug Development Department, Gustave Roussy, Villejuif, France. 11. Head and Neck and Thyroid Cancer Disease Sections, University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, PA, USA. 12. Georgia Cancer Center, Augusta University, Augusta, GA, USA. 13. Biostatistics, MedImmune, Gaithersburg, MD, USA. 14. Translational Sciences, MedImmune, Gaithersburg, MD, USA. 15. Clinical Development, MedImmune, Gaithersburg, MD, USA. 16. Tumor Immunotherapy Program, Princess Margaret Cancer Centre, Toronto, ON, Canada.
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.
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.
Authors: Rajaa El Meskini; Devon Atkinson; Alan Kulaga; Abdalla Abdelmaksoud; Michelle Gumprecht; Nathan Pate; Susana Hayes; Michael Oberst; Ian M Kaplan; Patrick Raber; Terry Van Dyke; Shyam K Sharan; Robert Hollingsworth; Chi-Ping Day; Glenn Merlino; Zoë Weaver Ohler Journal: Mol Cancer Res Date: 2021-04-22 Impact factor: 6.333