Dr Dasari on the Evolving Treatment Paradigm in mCRC

“We know from the trials that led to approval of [regorafenib and TAS-102 monotherapy] that the improvement in survival [with these agents] was incremental and their use was somewhat limited due to the adverse effect profiles, especially in the case of regorafenib…There's a huge unmet need, and it’s really exciting to see the approval of 2 new regimens in this disease.”

Arvind N. Dasari, MD, MS, associate professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the roles for fruquintinib (Fruzqala) and trifluridine/tipiracil (TAS-102; Lonsurf) plus bevacizumab (Avastin) in the current metastatic colorectal cancer (mCRC) treatment paradigm.

On November 8, 2023, fruquintinib received FDA approval for adult patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy; a VEGF inhibitor; and an EGFR inhibitor, if appropriate for those with RAS wild-type disease, Dasari begins. This approval was supported by data from the phase 3 FRESCO-2 (NCT04322539) and Chinese FRESCO (NCT02314819) trials, which demonstrated improved overall survival (OS) with fruquintinib plus best supportive care (BSC) compared with placebo plus BSC.

Earlier, on August 2, 2023, TAS-102 plus bevacizumab received FDA approval for patients with previously treated mCRC based on results from the phase 3 SUNLIGHT trial (NCT04737187), which showed improved median OS and progression-free survival with the combination compared with TAS-102 alone, he adds.

Prior to these FDA approvals, treatment options for refractory mCRC were limited to regorafenib (Stivarga) and TAS-102 monotherapy, both of which offered only incremental survival benefits, Dasari states. Use of regorafenib, in particular, was limited by its adverse effect profile, often necessitating dose reductions, he notes. The FRESCO-2 and SUNLIGHT trials provide evidence for more effective and tolerable regimens, each suited to specific patient populations, according to Dasari. Fruquintinib demonstrated efficacy in highly refractory patients who had progressed on all available therapies, including TAS-102 and regorafenib, and offers the convenience of an oral formulation, Dasari explains. Meanwhile, the combination of TAS-102 plus bevacizumab has become a standard for third-line therapy, though its infusion component may limit its appeal for some patients, he states.

The choice between these regimens depends on individual patient characteristics and treatment priorities, Dasari continues. TAS-102 plus bevacizumab may be preferred for patients without significant hematologic toxicity concerns who can manage an infusion schedule, Dasari says. Fruquintinib, on the other hand, is an all-oral option, making it suitable for patients with prior myelosuppression or those seeking a more convenient treatment modality, he asserts. Together, these treatment advances diminish the role of regorafenib in this setting, given the improved efficacy and tolerability of fruquintinib and the TAS-102 combination, Dasari concludes.