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

Kawazoe, A; Xu, RH; Garc&#237;a-Alfonso, P; Passhak, M; Teng, HW; Shergill, A; Gumus, M; Qvortrup, C; Stintzing, S; Towns, K; Kim, TW; Shiu, KK; Cundom, J; Ananda, S; Lebedinets, A; Fu, R; Jain, R; Adelberg, D; Heinemann, V; Yoshino, T; Elez, E; LEAP-017 Investigators

Author(s): Kawazoe, A; Xu, RH; García-Alfonso, P; Passhak, M; Teng, HW; Shergill, A; Gumus, M; Qvortrup, C; Stintzing, S; Towns, K; Kim, TW; Shiu, KK; Cundom, J; Ananda, S; Lebedinets, A; Fu, R; Jain, R; Adelberg, D; Heinemann, V; Yoshino, T; Elez, E; LEAP-017 Investigators;
Details: Publication Year 2024-08-20,Volume 42,Issue #24,Page 2918-2927
Journal Title: Journal of Clinical Oncology
Publication Type: Research article
Abstract: 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.
Publisher: American Society of Clinical Oncology
Keywords: Humans; *Phenylurea Compounds/administration & dosage/therapeutic use; *Colorectal Neoplasms/drug therapy/pathology/mortality; *Quinolines/administration & dosage/therapeutic use/adverse effects; *Antibodies, Monoclonal, Humanized/administration & dosage/therapeutic; use/adverse effects; Male; Female; Middle Aged; Aged; *Antineoplastic Combined Chemotherapy Protocols/therapeutic use/adverse effects; Standard of Care; Adult; Liver Neoplasms/secondary/drug therapy; Aged, 80 and over; Pyridines
Department(s): Medical Oncology
Publisher's Version: https://doi.org/10.1200/jco.23.02736
Open Access at Publisher's Site: https://doi.org/10.1200/jco.23.02736
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-09-12 06:49:06

Last Modified: 2024-09-12 06:49:36