Dr. Foote on the Quest to Determine Optimal Sequencing in Late-line mCRC

Micheal Foote, MD, medical oncologist, assistant attending physician, Memorial Sloan Kettering Cancer Center, discusses the quest to determine optimal sequencing of current therapeutics in the third-line setting and beyond for metastatic colorectal cancer (mCRC).

Findings from the phase 3 SUNLIGHT trial (NCT04737187), which is examining the use of trifluridine/tipiracil (TAS-102; Lonsurf) plus bevacizumab (Avastin) as a third-line treatment in patients with refractory mCRC were presented at the 2023 Gastrointestinal Cancers Symposium. Results demonstrated that the combination improved overall survival (OS) and disease control vs TAS-102 alone in this patient population, in all clinically relevant subgroups.

Based on these findings, the combination of TAS-102 and bevacizumab will likely continue as a standard third-line treatment after all acceptable targeted therapies have been exhausted, according to Foote. After patients have progressed on this regimen, they may receive regorafenib (Stivarga), followed by fruquintinib (Inrebic), Foote says. Attempts to create a definitive guideline on the optimal sequence of TAS-102 vs regorafenib in this setting are ongoing, he notes.

The emergence of fruquintinib may have addressed the need for a novel therapeutic option in the fourth line and beyond, Foote adds. In June 2020, the FDA granted a fast track designation to fruquintinib based on findings from the phase 3 FRESCO-2 study (NCT04322539). In this trial, treatment with fruquintinib resulted in a statistically significant improvement in OS, as well as progression-free survival, which served as a key secondary end point. The agent was deemed tolerable, and its safety profile was consistent with previously reported data.

Notably, a significant amount of the population in FRESCO-2 who responded to fruquintinib had previously progressed on TAS-102 and regorafenib, Foote emphasizes. This indicates that the regimen may be an optimal choice for these patients in later lines, he explains. The potential utility of fruquintinib in earlier lines of treatment is also an area of interest for continued research, Foote adds. The agent’s safety profile may be favorable compared with other VEGF inhibitors, which makes it an attractive option for further investigation in this space, he concludes.