Positive overall survival (OS) and quality of life (QOL) data with fruquintinib (Fruzaqla) in patients with advanced colorectal cancer (CRC) have positioned the agent as a valuable later-line therapy. The agent also serves as an important option to use as maintenance therapy as early as possible in each patient’s personalized treatment sequence, according to John Marshall, MD.
“You want to use this drug at some point in your patients [with CRC], because it [offers a] survival advantage,” Marshall said about fruquintinib in an interview with OncLive®. “Don’t leave it on the table.”
Fruquintinib was FDA approved in November 2023 for the treatment of adult patients with metastatic CRC (mCRC) who have previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy; VEGF-directed therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy.1 The regulatory decision was backed by data from 2 pivotal clinical trials. In the phase 3 FRESCO-2 trial (NCT04322539), the median OS was 7.4 months (95% CI, 6.7-8.2) with fruquintinib plus best supportive care (BSC; n = 461) vs 4.8 months (95% CI, 4.0-5.8) with placebo plus BSC (n = 230; HR, 0.66; 95% CI, 0.55-0.80; P < .001).1,2 In the phase 3 FRESCO trial (NCT02314819), the median OS was 9.3 months (95% CI, 8.2-10.5) in the fruquintinib arm (n = 278) vs 6.6 months (95% CI, 5.9-8.1) in the placebo arm (n = 138; HR, 0.65, 95% CI, 0.51-0.83; P < .001).
In the interview, Marshall contextualized these fruquintinib data in the mCRC treatment paradigm, which also includes trifluridine/tipiracil (Lonsurf; TAS-102) plus bevacizumab (Avastin) for the same indication as fruquintinib. This regimen was FDA approved in August 2023 based on data from the phase 3 SUNLIGHT trial (NCT04737187), in which TAS-102 plus bevacizumab (n = 246) elicited a median OS of 10.8 months (95% CI, 9.4-11.8) compared with 7.5 months (95% CI, 6.3-8.6) with TAS-102 alone (n = 246; HR, 0.61; 95% CI, 0.49-0.77; P < .001).3,4
In the interview, Marshall also explained the agent’s efficacy in later lines of CRC therapy based on clinical trial data, advocated for the agent’s use as maintenance therapy to avoid overtreatment, and stressed the importance of molecular profiling in patients at diagnosis in conjunction with robust multidisciplinary care during treatment.
Marshall is 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 in Washington, DC.
OncLive: What is the mechanism of action of fruquintinib?
Marshall: Fruquintinib targets VEGF receptors. A lot of drugs do that. This [drug] targets VEGF receptors 1, 2, and 3. The whole VEGF receptor pathway is important for angiogenesis, and maybe immunotherapy, [although the field is] skeptical on that end. [Fruquintinib has] tight binding to the receptor, blocking signaling, [similar to a] TKI.
Where does fruquintinib currently fit into the CRC treatment paradigm?
We know fruquintinib works because of the big, randomized studies that were done.
We know that some patients [will have] minor responses, but mostly a stable disease [SD] benefit is what you see from the drug. It’s oral, which makes for a nice break from intravenous [IV] therapy. [The data with this agent support the] VEGF [inhibition] beyond progression idea. [Fruquintinib is] approved in the third- or later-line settings.
What might be the role of fruquintinib earlier in the treatment paradigm?
I am a big believer in the concept of maintenance therapy. There are only a few drugs in the CRC treatment continuum that cause a regression: [certain chemotherapy regimens] and sometimes EGFR-directed therapies. Almost everything else is maintenance [therapy], or [treatments that elicit] SD.
Every chance I get to switch from the more intensive IV approaches to oral maintenance, I do it. I make sure to use fruquintinib before the patient is too burnt out. The one mistake oncologists make with this drug is holding off on it too long until the patient is too ill.
Which [regimen] you use first between TAS-102/bevacizumab and fruquintinib has a lot to do with the patient in front of you. There are patients in whom TAS-102/bevacizumab is the right [subsequent treatment], [and other times it’s] fruquintinib. [This decision is related to] tumor burden and the last treatment the patient received. There is no one right answer for that.
What clinical trial data help you decide when to use fruquintinib?
[In the FRESCO and FRESCO-2 trials], fruquintinib was tested against placebo [in patients with mCRC] and proved positive. [In the SUNLIGHT trial], TAS-102/bevacizumab was [tested] against TAS-102 alone [in patients with mCRC], and the TAS-102/bevacizumab combination showed positive data as well. We have these 2 strong choices for patients in the more refractory setting.
Do [patients] want to avoid coming into the clinic? How bad is their bone marrow? The adverse effects [AEs] associated with these medicines are different [from each other]. I try to pick the optimal treatment for the patient in front of me.
What QOL data have been reported with fruquintinib that may play a role in your treatment decision-making?
With all these drugs, we give high doses. The recommended phase 2 dose is often the maximum tolerated dose. At 5 mg daily with fruquintinib, most patients [tolerate the agent] well.
[AEs like] hypertension and fatigue happen [with fruquintinib]. Often, as with many drugs, some patients start at a lower dose [of fruquintinib] and inch their way up vs starting high and de-escalating. When you’re dosing this medicine, you want [to schedule a] quick follow-up with that patient [to make sure] you get the dose right.
Based on the available efficacy, safety, and QOL data with fruquintinib, how do you explain treatment goals to patients and approach shared decision-making with patients who may be eligible for this agent?
By the time you’re making these kinds of decisions, you know the patient well. You know their family. You know their priorities. They know your style. You know theirs.
Describe this treatment [the same way] you’ve already [described other treatments] before with them. Sometimes they’ve already done the research themselves. Sometimes you’re the first one to introduce it. Take your time. Give them the best information available. There are web-based resources as well. The patient [should become] the best consumer.
What unmet needs persist for patients with CRC?
The biggest new development in CRC is we have to perform molecular profiling in all patients from the beginning. We have [biomarkers including] BRAF, HER2, and microsatellite instability, and soon we may have RAS. We have to know [the patient’s] molecular profiling from the start.
A high percentage of patients don’t have a targetable lesion or will eventually need some of these serious [treatments] we’re talking about that are not targeted to a precision medicine target. You have to know what’s going on there. You have to [see whether] the patient has a surgical option, even in the metastatic setting. Different centers have different levels of expertise and comfort about [treating] and removing [tumors]. You want good, solid, multidisciplinary care.
Importantly, there is nothing magical. You don’t get an award for giving 12 cycles of chemotherapy. That’s a completely made-up number, and yet we feel like we have to give 12 cycles. All 12 cycles [results in] is [more] toxicity. Stop [chemotherapy] sooner. You’re not going to get an ongoing response; the response is going to stay stable. Switch to one of these other medicines. Use maintenance therapies more.
References
- FDA approves fruquintinib in refractory metastatic colorectal cancer. FDA. November 8, 2025. Accessed August 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fruquintinib-refractory-metastatic-colorectal-cancer
- Fruzaqla. Prescribing information. Takeda; 2025. Accessed August 19, 2025. https://www.fruzaqlahcp.com/sites/default/files/resources/fruzaqla-prescribing-information.pdf
- FDA approves trifluridine and tipiracil with bevacizumab for previously treated metastatic colorectal cancer. FDA. August 2, 2023. Accessed August 19, 2025. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-trifluridine-and-tipiracil-bevacizumab-previously-treated-metastatic-colorectal-cancer
- Lonsurf. Prescribing information. Taiho Oncology; 2023. Accessed August 19, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/207981s012lbl.pdf