What Should Patients With mCRC Consider When Deciding Treatment Options?

Trifluridine/tipiracil (Lonsurf) plus bevacizumab (Avastin) and fruquintinib (Fruzaqla) represent the cornerstone of the modern later-line treatment paradigm for metastatic colorectal cancer (mCRC). They necessitate a clinical strategy that balances efficacy data with individual patient priorities, according to Marwan G. Fakih, MD. In an interview with CancerNetwork®, Fakih emphasized that navigating the complexities of third-line therapy and beyond requires oncologists to act as guides, ensuring all active agents are utilized while mitigating the impact of treatment-related toxicities.

The decision-making process for later-line mCRC is increasingly driven by specific clinical end points, most notably disease control and progression-free survival (PFS). Fakih noted that for patients whose primary goal is achieving the highest probability of disease stabilization, the combination of trifluridine/tipiracil and bevacizumab serves as a vital clinical standard. Data from the phase 3 SUNLIGHT trial (NCT04737187), which evaluated trifluridine/tipiracil plus bevacizumab, support this approach for patients seeking to maintain a PFS end point at the critical 4-month mark.

While disease control is paramount, the mode of administration often dictates the therapeutic path. Fruquintinib offers a distinct advantage for patients who prioritize convenience and wish to transition away from intravenous infusions. However, Fakih cautioned that physiological factors, such as a baseline platelet count of 70,000, must inform the selection.

He also highlighted the safety findings from recent investigations, “The reassuring thing about SUNLIGHT is that the rates of febrile neutropenia were very low on the [trifluridine/tipiracil] plus bevacizumab arm. Really patients had an outside the bone marrow suppression and low rates of severe toxicities.”

Fakih is a professor in the department of Medical Oncology and Therapeutics Research, the deputy director of City of Hope Comprehensive Cancer Center, medical director for Briskin Center for Clinical Research, and division chief of Gastrointestinal Medical Oncology and co-director of the Gastrointestinal Cancer Program at City of Hope.

Transcript:

CancerNetwork: For patients with later-line mCRC, how do you aid in their treatment decision-making?

Fakih: It’s important to guide patients in your decision-making as well. Patients are looking at their physicians, seeking guidance. There are pros and cons for every strategy; the most important outcome is going to be eventually attained by making sure that all active agents are offered to your patients, and by also being mindful of what the patients’ priorities and goals are. Those could be variable from one patient to another. Some patients may say, “I don’t want to come for infusions anymore. I just want to take an oral medication.” That may be somebody who should be getting fruquintinib. Some patients, on the other hand, may be asking the question, “Which regimen has the highest disease control? What are the best chances that I maintain a PFS end point at the 4-month mark?” Numerically speaking, if we look at SUNLIGHT, that’s mostly with [trifluridine/tipiracil] and bevacizumab.

Quality of life is important. A lot of people flag [trifluridine/tipiracil] as an agent that is associated with bone marrow suppression, which is true; however, the reality is that neutropenia and leukopenia are blood tests, not a bad feeling. If your white [blood cell] count is low, that doesn’t mean you’re having severe fatigue. The reassuring thing about SUNLIGHT is that the rates of febrile neutropenia were very low on the [trifluridine/tipiracil] plus bevacizumab arm. Really patients had an outside the bone marrow suppression and low rates of severe toxicities. We’re privileged to have the option of using G-CSF support and maintaining treatment intensity in patients who are tolerating the treatment well otherwise. I have not seen resistance to using [trifluridine/tipiracil] plus bevacizumab map from my patients, and I’ve seen some fairly good results in disease control in patients who receive [this regimen] in the third-line setting. Are there patients who I think are better served with fruquintinib in that setting? If you have a patient who has a baseline platelet count of 70,000, that’s a patient who may have a hard time with thrombocytopenia during treatment and may be considered for other strategies in that scenario. It’s individualized and a patient discussion, and the physicians who know their patients best and have been treating them through that journey will be able to guide them to the best approach.

Reference

Prager GW, Elez E, Fakih MG, et al. Association between neutropenia and efficacy in patients with refractory mCRC receiving trifluridine/tipiracil + bevacizumab: post hoc analysis of the SUNLIGHT trial. ESMO Gastrointest Oncol. 2025;10:100234. Published online September 8, 2025. doi:10.1016/j.esmogo.2025.100234