Cathy Eng, MD, FACP, FASCO
Cathy Eng, MD, FACP, FASCO, the David H. Johnson Chair in Surgical and Medical Oncology, Professor of Medicine, Hematology and Oncology, Co-Director of GI Oncology and Co-Leader of the Gastrointestinal Cancer Research Program at Vanderbilt-Ingram Cancer Center, Nashville, commented that the failure of LEAP-017 to meet its primary endpoint of overall survival was “clearly disappointing.”
“The Kaplan-Meier curves for overall survival overlap fairly until 12 months, but then the sample size becomes significantly smaller. Based on these data, this combination should not be pursued in the general population of microsatellite instability–stable (MSI-S) refractory metastatic colorectal cancer,” Dr. Eng maintained. The phase III STELLAR 303 trial1 is evaluating a similar combination in the refractory setting—the multikinase inhibitor XL092 plus atezolizumab vs regorafenib—and these results should be informative, she said.
Dr. Eng made a few other points. Other phase II trials have suggested that immune checkpoint inhibition for patients with MSI-S disease is beneficial primarily in patients without liver metastases, though 70% of the LEAP-017 patients had liver metastases. She also pointed to a resurgence of interest, based on the phase II AtezoTRIBE study,2 in the role of the Immunoscore in identifying patients who are most likely to benefit from immune checkpoint inhibition, though validation in phase III trials is needed.
DISCLOSURE: Dr. Eng reported financial relationships with HUTCHMED and Merck.
REFERENCES
1. Hecht JR, Tabernero J, Parikh AR, et al: STELLAR-303: A phase 3 study of XL092 in combination with atezolizumab versus regorafenib in patients with previously treated metastatic colorectal cancer. 2023 ASCO Gastrointestinal Cancers Symposium. Abstract TPS267. Presented January 24, 2023.
2. Antoniotti C, Rossini D, Pietrantonio F, et al: Upfront FOLFOXIRI plus bevacizumab with or without atezolizumab in the treatment of patients with metastatic colorectal cancer (AtezoTRIBE): A multicentre, open-label, randomised, controlled, phase 2 trial. Lancet Oncol 23:876-887, 2022.
