Author(s): Akihito Kawazoe, MD1; Rui-Hua Xu, MD, PhD2; Pilar García-Alfonso, MD3; Maria Passhak, MD4; Hao-Wei Teng, MD, PhD5,6; Ardaman Shergill, MD7; Mahmut Gumus, MD8; Camilla Qvortrup, MD, PhD9; Sebastian Stintzing, MD10; Kathryn Towns, MD11; Tae Won Kim, MD12; Kai Keen Shiu, MD, PhD13; Juan Cundom, MD14; Sumitra Ananda, MD15; Andrey Lebedinets, MD16; Rong Fu, PhD17; Rishi Jain, MD18; David Adelberg, MD18; Volker Heinemann, MD, PhD19; Takayuki Yoshino, MD, PhD1; Elena Elez, MD, PhD20
PURPOSE
Treatment options are limited for patients with previously treated metastatic colorectal cancer (mCRC). In the LEAP-017 study, we evaluate whether lenvatinib in combination with pembrolizumab improves outcomes compared with standard of care (SOC) in previously treated mismatch repair proficient or not microsatellite instability high (pMMR or not MSI-H) mCRC.
METHODS
In this international, multicenter, randomized, controlled, open-label, phase III study, eligible patients age 18 years and older with unresectable, pMMR or not MSI-H mCRC, that had progressed on or after, or could not tolerate, standard treatment, were randomly assigned 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 400 mg intravenously once every 6 weeks or investigator’s choice of regorafenib or trifluridine/tipiracil (SOC). Randomization was stratified by presence or absence of liver metastases. The primary end point was overall survival (OS). LEAP-017 is registered at ClinicalTrials.gov (NCT04776148), and has completed recruitment.
RESULTS
Between April 8, 2021, and December 21, 2021, 480 patients were randomly assigned to lenvatinib plus pembrolizumab (n = 241) or SOC (n = 239). At final analysis (median follow-up of 18.6 months [IQR, 3.9]), median OS with lenvatinib plus pembrolizumab versus SOC was 9.8 versus 9.3 months (hazard ratio [HR], 0.83 [95% CI, 0.68 to 1.02]; P = .0379; prespecified threshold P = .0214). Grade ≥3 treatment-related adverse events occurred in 58.4% (lenvatinib plus pembrolizumab) versus 42.1% (SOC) of patients. Two participants died due to treatment-related adverse events, both in the lenvatinib plus pembrolizumab arm.
CONCLUSION
In patients with pMMR or not MSI-H mCRC that had progressed on previous therapy, there was no statistically significant improvement in OS after lenvatinib plus pembrolizumab treatment versus SOC. No new safety signals were observed.
Author Affiliations
1National Cancer Center Hospital East, Kashiwa, Japan; 2Department of Medical Oncology, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangdong, China; 3Medical Oncology Service, Hospital G. U. Gregorio Marañón, IiSGM, Universidad Complutense, Madrid, Spain; 4Rambam Health Care Campus-Oncology, Haifa, Israel; 5Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan; 6National Yang Ming Chiao Tung University, Hsinchu, Taiwan; 7University of Chicago Pritzker School of Medicine, Chicago, IL; 8Istanbul Medeniyet University Hospital, Istanbul, Turkey; 9Righospitalet, Copenhagen, Denmark; 10Department of Oncology, Rigshospitalet, Copenhagen, Denmark; 11North York General Hospital, Toronto, ON, Canada; 12Department of Oncology, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea; 13University College Hospital, NHS Foundation Trust, London, United Kingdom; 14Instituto de Diagnóstico e Investigaciones Metabólicas, Buenos Aires, Argentina; 15Peter MacCallum Cancer Centre and Epworth Healthcare, Melbourne, VIC, Australia; 16Leningrad Regional Clinical Oncology Dispensary, St Petersburg, Russia; 17MSD China, Shanghai, China; 18Merck & Co, Inc, Rahway, NJ; 19Comprehensive Cancer Center at Ludwig Maximilian University of Munich, Munich, Germany; 20Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain
