Pembrolizumab With or Without Lenvatinib as First-Line Therapy for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Phase III LEAP-010 Study
Abstract
PURPOSE The PD-1 inhibitor pembrolizumab is approved as first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). In LEAP-010 (ClinicalTrials.gov identifier: NCT04199104 ), the multikinase inhibitor lenvatinib plus pembrolizumab was evaluated as first-line therapy in participants with PD-L1 combined positive score (CPS) ≥1 R/M HNSCC. METHODS In this phase III, randomized, placebo-controlled, double-blind study, participants 18 years and older with PD-L1 CPS ≥1 R/M HNSCC deemed incurable by local therapy were randomly assigned 1:1 to lenvatinib 20 mg plus pembrolizumab 200 mg IV once every 3 weeks for ≤35 cycles or placebo orally once daily plus pembrolizumab 200 mg IV once every 3 weeks for ≤35 cycles. Primary end points were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Per the prespecified analysis plan, ORR and PFS were reported from the first interim analysis (IA1; data cutoff: July 6, 2022), and OS from IA2 (data cutoff: May 30, 2023). RESULTS Five hundred eleven participants were randomly assigned to lenvatinib plus pembrolizumab (n = 256) or placebo plus pembrolizumab (n = 255). The median time from random assignment to data cutoff was 11.5 months for IA1 and 21.3 months for IA2. At IA1, the median PFS was 6.2 months for lenvatinib plus pembrolizumab versus 2.8 months for placebo plus pembrolizumab (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.81]; P = .0001040); the ORR was 46.1% versus 25.4%, respectively (difference = 20.2% [95% CI, 10.5 to 29.6]; P = .0000251). At IA2, the median OS was 15.0 months for lenvatinib plus pembrolizumab versus 17.9 months for placebo plus pembrolizumab (HR,1.15 [95% CI, 0.91 to 1.45]; P = .882). At IA2, 170 (66.9%) participants receiving lenvatinib plus pembrolizumab had grade 3-4 all-cause adverse events compared with 97 (38.3%) participants on placebo plus pembrolizumab. CONCLUSION In participants with PD-L1 CPS ≥1 R/M HNSCC, first-line lenvatinib plus pembrolizumab significantly improved ORR and PFS, but not OS, compared with placebo plus pembrolizumab. The safety profile was consistent with published data.
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (172)
Thiago Bueno de Oliveira
AC Camargo Cancer Center, São Paulo, Brazil
Paul L. Swiecicki
Corina Dutcus
Eisai Inc, Nutley, NJ
Chinyere E. Okpara
Eisai Ltd., Hatfield, United Kingdom
Juan Shen
Department of Marine Pharmacy, School of Life Science and Biopharmaceutics, Guangdong Pharmaceutical University
Kimberly Benjamin
Merck, Rahway, NJ
Burak Gumuscu
Merck, Rahway, NJ
Robert I. Haddad
Hussein Soudy Hussein
Michael Boyer
Sydney Medical School, University of Sydney
Anne Taylor
Julia Pastorello
Marcio Costa
Adriana Valadares
Thiago Oliveira
Luciano Viana
Karine da Trindade
Gustavo Alves
Anna Spreafico
Olivier Dumas
7CHU de Quebec-Universite Laval, Quebec, Canada
Nathaniel Bouganim
McGill University Health Centre, Montreal, QC, Canada
Ye Guo
Qingyuan Zhang
Department of Oncology, Harbin Medical University Cancer Hospital, Harbin, China
Meiyu Fang
Zhejiang Cancer Hospital, Hangzhou, China
Ning Jia
Liangfang Shen
Kunyu Yang
Nianyong Chen
Hui Wu
Ying Cheng
Institute of Biomedical Research, Yunnan University
Zhijun Yuan
Xiangqian Zheng
Jingao Li
Yan Sun
Guangyuan Hu
Song Qu
Chaosu Hu
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
Sufang Qiu
Zhenhua Li
State Key Laboratory of Forage Breeding-by-Design and Utilization, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences
Shaoqiang Zhang
Feng Jin
School of Advanced Materials
Guoxin Ren
Jin Gao
Jinguan Lin
Xiaoming Huang
Jinsong Li
Xujing Lu
Shurong Zhang
National Key Laboratory of Agricultural Microbiology, College of Life Science and Technology, Huazhong Agricultural University
Wenbin Lei
Jérôme Fayette
Sébastien Salas
Assistance Publique Hopitaux de Marseille, Marseille, France
Florian Clatot
Asmahane Benmaziane Teillet
Caroline Even
Daniel Heudobler
University Hospital Regensburg, Regensburg, Germany
Simon Laban
Department of Otorhinolaryngology and Head and Neck Surgery, Ulm University Medical Center and Comprehensive Cancer Center Ulm, Ulm, Germany
Daniela Dörfel
Martin Mueller
19Clinic for Hematology, Oncology and Immunology, Klinikum Siloah Hannover, Hannover, Germany
Kim Marienhagen
Andreas Dietz
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Leipzig, Leipzig, Germany
David Zurmeyer
Christian Brandts
12Department of Medicine, Hematology/Oncology, Goethe University Hospital Frankfurt, Frankfurt, Germany
Tobias Albrecht
Paul-Stefan Mauz
Department of Otolaryngology, Head and Neck Surgery, University Hospital Tübingen, Tübingen, Germany
Jens Klussmann
Konrad Klinghammer
Sebastian Ochsenreither
Tibor Csoszi
Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary
Laszlo Landherr
Erika Hitre
Gergely Dombovari
Peter Arkosy
Judit Oláh
Lisa Licitra
Marco Benasso
Vittorio Ferrari
Maria Ghi
Martina Violati
Franco Nole
Makoto Tahara
Sadakatsu Ikeda
Yoshitaka Honma
Shunji Takahashi
Natural Product Biosynthesis Research Unit, RIKEN Center for Sustainable Resource Science
Nobuhiko Oridate
Tomoya Yokota
Shizuoka Cancer Center, Shizuoka, Japan
Naoki Nishio
Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Aichi, Japan
Kaoru Tanaka
Kindai University Hospital, Sakai, Japan
Akihito Tsuji
Department of Clinical Oncology, Kagawa University Faculty of Medicine, Kita-Gun, Japan
Tsutomu Ueda
Hiroshima University Hospital, Hiroshima, Japan
Takashi Kinoshita
Torahiko Nakashima
Takuma Onoe
Department of Medical Oncology, Hyogo Cancer Center, Akashi-Shi, Japan
Shigenori Kadowaki
Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
Victor Oyervides Juarez
Carlos Hernandez Hernandez
Marinee Torres
Jorge Martinez Rodriguez
Daniel Motola Kuba
Dency Milla
Mivael Olivera Hurtado de Mendoza
Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru
Walter Li Torres
Jose Salinas Paz
Carmen Acevedo
Boguslawa Karaszewska
Department of Oncology, Regional Polyclinical Hospital in Konin, Konin, Poland
Piotr Koralewski
Dorota Filarska
Tomasz Rutkowski
Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland
Izabella Debicka
Bogdan Zurawski
Department of Outpatient Chemotherapy, Professor Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland
Jacek Mackiewicz
Cancer Genetic Laboratory, Greater Poland Cancer Centre, Poznan, Poland
Andrzej Kawecki
Anna Kedrova
Mikhail Klochikhin
Yaroslavl Regional SBIH Clinical Oncology Hospital, Yaroslavl, Russian Federation
Sufia Safina
Denis Tantsyrev
Hyun Woo Lee
Sung-Bae Kim
Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
Sang Hee Cho
Department of Internal Medicine, Chonnam National University Medical School, Gwangju, South Korea
Keon Uk Park
Yoon Ho Ko
Keun-Wook Lee
Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, South Korea
Irene Brana García
Marc Oliva Bernal
Lara Iglesias Docampo
Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain
Julio Lambea Sorrosal
Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
Manuel Chaves Conde
Beatriz Castelo Fernandez
Ruey-Long Hong
Muh-Hwa Yang
Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan
Yi-Fang Chang
Chia-Jui Yen
Shau-Hsuan Li
Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Ahmet Bilici
Muhammet Hacioglu
Muhammed Akinci
Hakan Harputluoglu
Saziye Burcak Karaca
Sercan Aksoy
Cagatay Arslan
Jessica Mason
Kevin Chiu
Robert Metcalf
The Christie NHS Foundation Trust, Manchester, United Kingdom
Kevin Harrington
Rafael Moleron Mancebo
Matthew Griffin
Northwell Health, Manhasset, New York, United States
Teresa Guerrero Urbano
Jawad Sheqwara
Robert Alter
Justine Bruce
Patrick Cobb
John Deeken
Achuta Guddati
Jerome Goldschmidt
Elizabeth Gunderson
Robert Haddad
Upendra Hegde
Antonio Jimeno
Robert Lemon
Steven McCune
6Wellstar Health System, Marietta, United States
Prakash Neupane
Doru Paul
Weill Cornell Medical College, New York, NY
Jameel Muzaffar
Rebecca Redman
Matthew Taylor
University of Colorado, Anschutz, Medical Center, Aurora
Abirami Sivapiragasam
Medical University of South Carolina, Charleston, SC
Yungpo Su
Head and Neck Medical Oncology, Nebraska Cancer Specialists, Omaha, NE
Ammar Sukari
Karmanos Cancer Institute, Detroit, MI
Siddharth Sheth
Division of Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC
Alberto Bessudo
Douglas Adkins
Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Washington University School of Medicine, Alvin J. Siteman Cancer Center, and Barnes–Jewish Hospital, St. Louis
Paul Swiecicki
Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan Rogel Cancer Center, Ann Arbor, MI
Matthew Salzberg