Dan P Zandberg1, Alain P Algazi2, Antonio Jimeno3, James S Good4, Jérôme Fayette5, Nathaniel Bouganim6, Neal E Ready7, Paul M Clement8, Caroline Even9, Raymond W Jang10, Stuart Wong11, Ulrich Keilholz12, Jill Gilbert13, Moon Fenton14, Irene Braña15, Stephanie Henry16, Eva Remenar17, Zsuzsanna Papai18, Lillian L Siu10, Anthony Jarkowski19, Jon M Armstrong19, Kobby Asubonteng19, Jean Fan19, Giovanni Melillo19, Ricard Mesía20. 1. University of Pittsburgh Medical Center, Hillman Cancer Center, Pittsburgh, PA, USA. Electronic address: zandbergdp@upmc.edu. 2. University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA. 3. Division of Medical Oncology, University of Colorado School of Medicine, Aurora, CO, USA. 4. Institute of Head and Neck Studies and Education, Queen Elizabeth Hospital, Birmingham, UK. 5. Clinical Oncology, Cancer Center Centre Léon Bérard, University of Lyon, Lyon, France. 6. Department of Oncology, McGill University Health Centre, Montréal, QC, Canada. 7. Duke University Medical Center, Durham, NC, USA. 8. Department of Oncology, Leuven Cancer Institute, KU Leuven, Belgium. 9. Department of Head and Neck Oncology, Institut Gustave Roussy, Villejuif, France. 10. Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada. 11. Division of Hematology Oncology, Medical College of Wisconsin, Milwaukee, WI, USA. 12. Charité Comprehensive Cancer Center, Berlin, Germany. 13. Henry-Joyce Cancer Clinic, Nashville, TN, USA. 14. The West Cancer Center, University of Tennessee Health Science Center, Memphis, TN, USA. 15. Medical Oncology Department, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona, Barcelona, Spain. 16. Department of Oncology-Hematology, Radiotherapy, and Nuclear Medicine, CHU UCL Namur, Namur, Belgium. 17. National Institute of Oncology (Országos Onkológiai Intézet), Budapest, Hungary. 18. State Health, Center Higatian Defanse Forses, Budapest, Hungary. 19. AstraZeneca, Gaithersburg, MD, USA. 20. Medical Oncology Department, Catalan Institute of Oncology, University of Barcelona, IDIBELL, Barcelona, Spain.
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.
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.
Authors: P Urwyler; I Earnshaw; M Bermudez; E Perucha; W Wu; S Ryan; L Mcdonald; S N Karagiannis; L S Taams; N Powell; A Cope; S Papa Journal: Clin Exp Immunol Date: 2020-02-21 Impact factor: 4.330
Authors: Shannon M Clayton; Joehleen A Archard; Joseph Wagner; D Gregory Farwell; Arnaud F Bewley; Angela Beliveau; Andrew Birkeland; Shyam Rao; Marianne Abouyared; Peter C Belafsky; Johnathon D Anderson Journal: Stem Cells Dev Date: 2020-01-30 Impact factor: 3.272
Authors: Robert L Ferris; William C Spanos; Rom Leidner; Anthony Gonçalves; Uwe M Martens; Chrisann Kyi; William Sharfman; Christine H Chung; Lot A Devriese; Helene Gauthier; Simon I Chiosea; Lazar Vujanovic; Janis M Taube; Julie E Stein; Jun Li; Bin Li; Tian Chen; Adam Barrows; Suzanne L Topalian Journal: J Immunother Cancer Date: 2021-06 Impact factor: 12.469