Dr Marshall on the Role of Fruquintinib in the Treatment Paradigm for mCRC

“You want to use this drug at some point in your patients, because it [offers a] survival advantage, so don’t leave it on the table. The one mistake oncologists make with this drug is holding off on it too long until the patient is too sick.”

John L. Marshall, MD, clinical director of oncology at Georgetown University Hospital, as well as chief of Hematology and Oncology, a professor of medicine and oncology, and director of the Otto J Ruesch Center for the Cure of Gastrointestinal Cancers at Georgetown Lombardi Comprehensive Cancer Center, discussed the role of fruquintinib (Fruzaqla) in the treatment paradigm for metastatic colorectal cancer (mCRC).

Findings from pivotal randomized trials established the efficacy of fruquintinib—a highly selective oral tyrosine kinase inhibitor of VEGF receptors 1, 2, and 3—in patients with refractory disease. The agent demonstrated a survival advantage compared with placebo and has been approved for use in the third-line setting and beyond, where it primarily achieves disease stabilization rather than objective tumor regression, Marshall explained.

According to Marshall, the oral formulation of fruquintinib offers a practical advantage in later lines of therapy, allowing patients to transition from intravenous chemotherapy to a maintenance-oriented regimen. He emphasized that the key clinical consideration is timing, noting that one of the most frequent clinical mistakes is delaying fruquintinib initiation until patients are too ill to derive meaningful benefit. Used appropriately, the therapy provides a survival benefit that should not be left unused in eligible patients, he stated.

Regarding sequencing, Marshall highlighted the ongoing clinical question of whether fruquintinib should be considered before trifluridine/tipiracil (Lonsurf; TAS-102), with or without bevacizumab (Avastin). He explained that this decision is highly patient-specific, depending on tumor burden, prior lines of therapy, and overall clinical status. Although TAS-102 plus bevacizumab remains a strong option in many cases, fruquintinib provides a distinct mechanism of action and oral convenience, making it a viable alternative, he stated. Marshall compared treatment sequencing to making a chess move, where the best option is determined by the patient’s overall clinical context rather than a fixed treatment algorithm.

At present, clinical data support the use of fruquintinib primarily in the later-line setting, and there is insufficient evidence to recommend its routine incorporation earlier in the treatment continuum ahead of TAS-102, according to Marshall. However, Marshall suggested that fruquintinib’s tolerability and mechanism raise the possibility that future studies could explore the earlier integration of this agent in the therapeutic sequence. For now, sequencing decisions should remain individualized, guided by patient characteristics and prior treatment history, he concluded.