Health-related quality of life outcomes from KEYNOTE-412: Chemoradiotherapy with or without pembrolizumab in participants with head and neck squamous cell carcinoma

Jean-Pascal Machiels^1*Yungan Tao²Lisa Licitra³Barbara Burtness⁴Makoto Tahara⁵Danny Rischin⁶Gustavo V. Alves⁷Iane Pinto Figueiredo Lima⁸Brett G. M. Hughes⁹Yoann Pointreau¹⁰Sercan Aksoy¹¹Simon Laban¹²Richard Greil¹³Martin Burian¹⁴Marcin Hetnal¹⁵Jean-Pierre Delord¹⁶Ricard Mesia¹⁷Miren Taberna¹⁸John Waldron¹⁹Christian Simon²⁰Vincent Gregoire²¹Kevin Joseph Harrington²²Christopher M. Black²³Josephine M Norquist²³Anran Wang²³Burak Gumuscu²³Behzad Bidadi²³Lillian L Siu²⁴

• ¹Cliniques Universitaires Saint-Luc and Institut de Recherche Expérimentale et Clinique (Pole MIRO), UCLouvain, Brussels, Belgium
• ²Gustave Roussy, Villejuif, France
• ³Fondazione IRCCS Istituto Nazionale dei Tumori and University of Milan, Milan, Italy
• ⁴Yale University School of Medicine and Yale Cancer Center, New Haven, United States
• ⁵National Cancer Center Hospital East, Kashiwa, Japan
• ⁶Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia
• ⁷Centro Integrado de Pesquisa em Oncología, Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil
• ⁸CRIO Centro Regional Integrado de Oncología, Fortaleza, Brazil
• ⁹Royal Brisbane and Women’s Hospital and University of Queensland, Brisbane, Australia
• ¹⁰Centre Jean Bernard Institut Inter-régionaL de Cancérologie, Centre de Cancérologie de la Sarthe, Le Mans, France
• ¹¹Hacettepe University Cancer Institute, Ankara, Türkiye
• ¹²Head & Neck Cancer Center of the Comprehensive Cancer Center Ulm, Ulm University Medical Center, Ulm, Germany
• ¹³Paracelsus Medical University, Salzburg Cancer Research Institute, and Cancer Cluster Salzburg, Salzburg, Austria
• ¹⁴Krankenhaus der Barmherzigen Schwestern Linz, Linz, Austria
• ¹⁵Andrzej Frycz Modrzewski Krakow University, Amethyst Radiotherapy Center, Rydygier Hospital, Krakow, Poland
• ¹⁶European Cancer Organisation, Brussels, Belgium
• ¹⁷Catalan Institut of Oncology, Barcelona, Spain
• ¹⁸Savana, Madrid, Spain
• ¹⁹Princess Margaret Cancer Centre, Toronto, Canada
• ²⁰University Medical Center Vaud (CHUV) - Lausanne University Hospital, Lausanne, Switzerland
• ²¹Léon Bérard Cancer Center, Lyon, France
• ²²The Institute of Cancer Research, London, United Kingdom
• ²³Merck & Co Inc, Rahway, United States
• ²⁴Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada

The health-related quality of life (HRQoL) of patients with locally advanced head and neck squamous cell carcinoma (LA HNSCC) is impacted by both disease-and treatment-related factors. Treatments that preserve and maximize HRQoL in this setting represent a substantial unmet need.: KEYNOTE-412 (NCT03040999) was a randomized, double-blind, placebocontrolled phase 3 study of pembrolizumab plus chemoradiotherapy (CRT) versus placebo plus CRT for maintenance therapy in participants with treatment-naïve LA HNSCC. Patientreported outcomes (PROs) assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EORTC QLQ Head and Neck 35 (H&N35) were pre-specified secondary endpoints and administered at baseline and throughout the study. Least squares mean (LSM) change from baseline was assessed using a constrained longitudinal data analysis model. No formal statistical significance testing was performed.The PRO analysis population included 395 participants randomized to receive pembrolizumab plus CRT and 397 to receive placebo plus CRT. Completion rates for all assessed PROs were >95% at baseline and >66% at week 45. LSM change from baseline to week 45 was similar between groups across EORTC QLQ-C30 and QLQ-H&N35 subscale scores. There were no notable differences in empirical mean change or the proportion of participants with improvement, stability, or deterioration from baseline to week 45 between treatment groups.The addition of pembrolizumab to CRT did not meaningfully impact HRQoL in participants with LA HNSCC.