Dr Hays on the Evolution of Later-line Treatment Options in Refractory mCRC

John L. Hays, MD, PhD, assistant professor, Department of Internal Medicine, The Ohio State University, member, Translational Therapeutics Program, The Ohio State University Comprehensive Cancer Center (OSUCC)–James, discusses the evolution of the treatment paradigm for patients with metastatic colorectal cancer (mCRC) who experience disease progression following standard chemotherapy regimens.

Traditionally, patients with mCRC who progressed on FOLFOX, FOLFOXIRI, or 5-fluorouracil (5-FU)–based regimens lacked effective treatment options in later lines, Hays begins. Many of these patients still exhibited acceptable fitness, but progressed on all available therapeutic options and could no longer be treated, he states. However, several recent advancements have expanded options for this patient population, including the breakthrough approval of tucatinib (Tukysa) and trastuzumab (Herceptin) for those with HER2-positive mCRC in January 2023.

Moreover, several novel treatment approaches are being evaluated for this patientpopulation including alternative methods of VEGF- and KRAS-inhibition, Hays continues.

The VEGF inhibitor fruquintinib (HMPL-013) previously received fast-track designation from the FDA in 2020 for patients with mCRC who had received prior fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, VEGF-directed therapy, and RAS wild-type, EGFR-directed therapy. An application for FDA approval was submitted based on data from the randomized phase 3 FRESCO-2 trial (NCT04322539) for patients with refractory mCRC, Hays adds. This trial showed that fruquintinib plus best supportive care improved the median overall survival from 4.8 months with placebo to 7.4 months, meeting the trial’s primary end point.

Additionally, some patients with mCRC may benefit from the approval of KRAS inhibitors in this space, Hays says. Almost half of patients with CRC exhibit KRAS mutations, which are associated with resistance to many current targeted therapies. Increasing the focus on developing agents that target other KRAS mutations more commonly found in CRC through clinical trials could improve outcomes for this subgroup, Hays concludes.