Danny Rischin1, Kevin J Harrington2, Richard Greil3, Denis Soulières4, Makoto Tahara5, Gilberto de Castro6, Amanda Psyrri7, Irene Braña8, Prakash Neupane9, Åse Bratland10, Thorsten Fuereder11, Brett G M Hughes12, Ricard Mesía13, Nuttapong Ngamphaiboon14, Tamara Rordorf15, Wan Zamaniah Wan Ishak16, Ruey-Long Hong17, René Gonzalez Mendoza18, Liyi Jia19, Diana Chirovsky20, Josephine Norquist21, Fan Jin22, Barbara Burtness23. 1. Medical Oncology, Peter MacCallum Cancer Centre and University of Melbourne, 305 Grattan Street, Melbourne, VIC 3000, Australia. Electronic address: danny.rischin@petermac.org. 2. Radiotherapy and Imaging, The Institute of Cancer Research/The Royal Marsden NHS Foundation Trust, National Institute for Health Research Biomedical Research Centre, 15 Cotswold Road, London SM2 5NG, United Kingdom. Electronic address: kevin.harrington@icr.ac.uk. 3. Hematology and Medical Oncology, Paracelsus Medical University, Salzburg Cancer Research Institute, and Cancer Cluster Salzburg, Hellbrunner Strasse 34, Salzburg 5020, Austria. Electronic address: r.greil@salk.at. 4. Haematology/Oncology, Centre Hospitalier de l'Université de Montréal, 1000 Saint Denis Street, Montreal, QC H2X 0C1, Canada. Electronic address: denis.soulieres.chum@ssss.gouv.qc.ca. 5. Head and Neck Medical Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoba, Kashiwa 277-8577, Japan. Electronic address: matahara@east.ncc.go.jp. 6. Medical Oncology, Instituto do Câncer do Estado de São Paulo, Av. Dr. Arnaldo, 251-Cerqueira César, São Paulo, 01246-000, Brazil. Electronic address: gilberto.castro@hc.fm.usp.br. 7. Medical Oncology, National and Kapodistrian University of Athens, Attikon University Hospital, Athens 157 72, Athens, Greece. Electronic address: psyrri237@yahoo.com. 8. Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Passeig de la Vall d'Hebron, 119-129, 08035 Barcelona, Spain. Electronic address: ibrana@vhio.net. 9. Hematology/Oncology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, MO 66160, USA. Electronic address: pneupane@kumc.edu. 10. Head & Neck Oncology, Oslo University Hospital, Bygg 19, Oslo, Norway. Electronic address: brt@ous-hf.no. 11. Medicine I, Medical University of Vienna, Spitalgasse 23, 1090 Vienna, Austria. Electronic address: thorsten.fuereder@meduniwien.ac.at. 12. Clinical Research Unit, Medical Oncology, Royal Brisbane & Women's Hospital and The University of Queensland, Butterfield Street, Ground Floor, Building 34, Herston, Queensland 4029, Australia. Electronic address: brett.hughes@health.qld.gov.au. 13. Head and Neck, Catalan Institute of Oncology, L'Hospitalet de Llobregat, Hospital Duran i Reynals, Avinguda de la Gran Via de l'Hospitalet, 199-203, 8908 Barcelona, Spain. Electronic address: rmesia@iconcologia.net. 14. Medicine, Ramathibodi Hospital, Mahidol University, 270 Rama 6 Road, Ratchathewi, Bangkok 10400, Thailand. Electronic address: ngamphaiboon@gmail.com. 15. Oncology, University Hospital, Raemistrasse 100, Zurich, Switzerland. Electronic address: tamara.rordorf@usz.ch. 16. Clinical Oncology Unit, Faculty of Medicine, University of Malaya, Jalan Universiti, 50603 Kuala Lumpur, Wilayah Persekutuan, Malaysia. Electronic address: wzamaniah@ummc.edu.my. 17. Oncology, National Taiwan University Hospital, No.1, Changde St. Zhongzheng Dist, Taipei 10048, Taiwan. Electronic address: rlhong@ntu.edu.tw. 18. Surgical Oncology, Centro Estatal de Cancerológia de Chihuahua, C. Ejercito Mexicano 3700, 31000 El Bajo, Chihuahua, Mexico. Electronic address: dr_renegonzalez@hotmail.com. 19. Merck Research Labs, Merck & Co. Inc, 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: liyi.jia@merck.com. 20. Merck Research Labs, Merck & Co. Inc, 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: diana.chirovsky@merck.com. 21. Merck Research Labs, Merck & Co. Inc, 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: josephine_norquist@merck.com. 22. Merck Research Labs, Merck & Co. Inc, 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: fan.jin@merck.com. 23. Medical Oncology, Yale University School of Medicine and Yale Cancer Center, 35 York Street, PO Box 208028, New Haven, CT 06510, USA. Electronic address: barbara.burtness@yale.edu.
Abstract
OBJECTIVES: To assess health-related quality of life (HRQoL) with first-line pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) in the phase 3 KEYNOTE-048 trial (NCT02358031). MATERIALS AND METHODS: HRQoL was measured using the European Organisation for Research and Treatment of Cancer 30-question quality-of-life (EORTC QLQ-C30), the EORTC 35-question quality-of-life head and neck cancer-specific module (EORTC QLQ-H&N35), and the EuroQol 5-dimension 3-level instruments (EQ-5D-3L). Secondary endpoints included mean change from baseline in EORTC QLQ-C30 global health status/quality of life (GHS/QoL) at week 15 and time to deterioration (TTD) in EORTC QLQ-C30 GHS/QoL and EORTC QLQ-H&N35 pain and swallowing. RESULTS: Of 882 enrolled participants, 844 received ≥ 1 dose of study treatment and completed ≥ 1 HRQoL assessment; adherence was ≥ 79% at week 15 across treatment groups. At week 15, EORTC QLQ-C30 GHS/QoL scores remained stable; no clinically meaningful between-group differences were observed (least squares mean difference, pembrolizumab vs cetuximab-chemotherapy, 0.24; 95% CI, -3.34 to 3.82; pembrolizumab-chemotherapy vs cetuximab-chemotherapy, 0.40; 95% CI, -3.46 to 4.26). Median TTD in EORTC QLQ-C30 GHS/QoL and EORTC QLQ-H&N35 pain and swallowing scores was not reached over 51 weeks across groups, showing stable HRQoL. TTD was similar between groups for EORTC QLQ-C30 GHS/QoL (pembrolizumab vs cetuximab-chemotherapy: HR, 1.38; 95% CI, 0.95-2.00; pembrolizumab-chemotherapy vs cetuximab-chemotherapy: HR, 1.37; 95% CI, 0.94-2.00), as was TTD in EORTC QLQ-H&N35 pain and swallowing scores. CONCLUSIONS: Pembrolizumab monotherapy and pembrolizumab-chemotherapy extended OS while maintaining HRQoL, further supporting first-line use for R/M HNSCC.
OBJECTIVES: To assess health-related quality of life (HRQoL) with first-line pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) in the phase 3 KEYNOTE-048 trial (NCT02358031). MATERIALS AND METHODS: HRQoL was measured using the European Organisation for Research and Treatment of Cancer 30-question quality-of-life (EORTC QLQ-C30), the EORTC 35-question quality-of-life head and neck cancer-specific module (EORTC QLQ-H&N35), and the EuroQol 5-dimension 3-level instruments (EQ-5D-3L). Secondary endpoints included mean change from baseline in EORTC QLQ-C30 global health status/quality of life (GHS/QoL) at week 15 and time to deterioration (TTD) in EORTC QLQ-C30 GHS/QoL and EORTC QLQ-H&N35 pain and swallowing. RESULTS: Of 882 enrolled participants, 844 received ≥ 1 dose of study treatment and completed ≥ 1 HRQoL assessment; adherence was ≥ 79% at week 15 across treatment groups. At week 15, EORTC QLQ-C30 GHS/QoL scores remained stable; no clinically meaningful between-group differences were observed (least squares mean difference, pembrolizumab vs cetuximab-chemotherapy, 0.24; 95% CI, -3.34 to 3.82; pembrolizumab-chemotherapy vs cetuximab-chemotherapy, 0.40; 95% CI, -3.46 to 4.26). Median TTD in EORTC QLQ-C30 GHS/QoL and EORTC QLQ-H&N35 pain and swallowing scores was not reached over 51 weeks across groups, showing stable HRQoL. TTD was similar between groups for EORTC QLQ-C30 GHS/QoL (pembrolizumab vs cetuximab-chemotherapy: HR, 1.38; 95% CI, 0.95-2.00; pembrolizumab-chemotherapy vs cetuximab-chemotherapy: HR, 1.37; 95% CI, 0.94-2.00), as was TTD in EORTC QLQ-H&N35 pain and swallowing scores. CONCLUSIONS: Pembrolizumab monotherapy and pembrolizumab-chemotherapy extended OS while maintaining HRQoL, further supporting first-line use for R/M HNSCC.
Keywords:
Chemotherapy head and neck neoplasms; Immunotherapy; Patient reported outcome measures; Pembrolizumab; Phase III clinical trial; Quality of life; Squamous cell carcinoma of head and neck