Episode 2: LEAP 017 – study: efficacy and safety of lenvatinib + pembrolizumab versus standard-of-care in previously treated mCRC
Presented by Prof Eric Van Cutsem (University Hospitals Leuven) and Prof Marc Van den Eynde (Cliniques Universitaires Saint-Luc)
The LEAP-017 study represents an exploration into the application of immunotherapy for refractory metastatic colorectal cancer, a domain where therapeutic options are limited. This randomised phase 3 trial, presented at the ESMO World Congress in Barcelona, aimed to elucidate the efficacy of immunotherapeutic interventions in patients unresponsive to conventional treatments.
Conducted as a third-line study, LEAP-017 enrolled patients with metastatic colorectal cancer resistant to standard agents such as oxaliplatin, irinotecan, and 5FU. Randomisation occurred between the standard arm (regorafenib or trifluridine/tiparacil) and the experimental arm (lenvatinib and pembrolizumab). The primary endpoint, overall survival, served as the linchpin for evaluating treatment efficacy.
Despite the study’s overall negative classification, a closer examination of the data reveals intriguing nuances. While the combination of pembrolizumab and lenvatinib did not attain statistical significance, a discernible trend emerged, indicating a 20% reduction in the risk of death. Subgroup analysis highlighted a potential benefit in patients lacking liver metastasis, introducing a novel dimension to the interpretation of outcomes.
LEAP-017 underscores the imperative of meticulous patient selection in the realm of immunotherapy for metastatic colorectal cancer. The identification of potential benefits in the subgroup without liver metastasis prompts a reconsideration of patient stratification for future trials. Moreover, the study accentuates the intricate interplay between liver metastasis and systemic immune microenvironments.
In the LEAP-017 study, the intersection of immunotherapy and refractory metastatic colorectal cancer presents a complex narrative. Beyond the apparent negativity, the study serves as a stepping stone, providing valuable insights into potential benefits and emphasising the pivotal role of precise patient selection in advancing therapeutic interventions in this demanding clinical context.
References:
A. Kawazoe et al., Lenvatinib plus pembrolizumab versus standard of care for previously treated metastatic colorectal cancer (mCRC): the phase 3 LEAP-017 study; Annals of Oncology, volume 34, sup 1, S179, 2023