Lenvatinib Plus Pembrolizumab Versus Standard of Care for Previously Treated Metastatic Colorectal Cancer: Final Analysis of the Randomized, Open-Label, Phase III LEAP-017 Study.
Akihito Kawazoe, Rui-Hua Xu, Pilar García-Alfonso, Maria Passhak, Hao-Wei Teng, Ardaman Shergill, Mahmut Gumus, Camilla Qvortrup, Sebastian Stintzing, Kathryn Towns, Tae Won Kim, Kai Keen Shiu, Juan Cundom, Sumitra Ananda, Andrey Lebedinets, Rong Fu, Rishi Jain, David Adelberg, Volker Heinemann, Takayuki Yoshino, Elena Elez, LEAP-017 Investigators
Author Information
Akihito Kawazoe: National Cancer Center Hospital East, Kashiwa, Japan. ORCID
Rui-Hua Xu: Department of Medical Oncology, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangdong, China. ORCID
Pilar García-Alfonso: Medical Oncology Service, Hospital G. U. Gregorio Marañón, IiSGM, Universidad Complutense, Madrid, Spain. ORCID
Maria Passhak: Rambam Health Care Campus-Oncology, Haifa, Israel.
Hao-Wei Teng: Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan.
Ardaman Shergill: University of Chicago Pritzker School of Medicine, Chicago, IL. ORCID
Mahmut Gumus: Istanbul Medeniyet University Hospital, Istanbul, Turkey. ORCID
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]; = .0379; prespecified threshold = .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.
Associated Data
ClinicalTrials.gov | NCT04776148
References
JAMA Oncol. 2023 May 1;9(5):627-634
[PMID: 36892833]
