Fruquintinib Provides Significant Survival Benefits in Heavily Pretreated mCRC

Sep 26, 2022

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Nageshwara Arvind Dasari, MD, discusses the results of the phase 3 FRESCO-2 trial of fruquintinib in patients with refractory metastatic colorectal cancer, the significance of the data for the treatment paradigm, and the potential next steps for examining the agent in this disease.

Nageshwara Arvind Dasari, MD

Fruquintinib (HMPL-013) resulted in a significant and clinically meaningful improvement in survival vs placebo in heavily pretreated patients with metastatic colorectal cancer (mCRC), according to data from the phase 3 FRESCO-2 trial (NCT04322539). These data support the consideration of this drug as a new treatment option for this population, according to Nageshwara Arvind Dasari, MD.

Data presented at the 2022 ESMO Congress showed that the trial met its primary end point of overall survival (OS) and key secondary end point of progression-free survival (PFS). Patients treated with fruquintinib achieved a median OS of 7.4 months (95% CI, 6.7-8.2) vs 4.8 months (95% CI, 4.0-5.8) with placebo (HR, 0.662; 95% CI, 0.549-0.800; P < .001). Moreover, treatment with fruquintinib resulted in a median PFS of 3.7 months (95% CI, 3.5-3.8) vs 1.8 months (95% CI, 1.8-1.9) with placebo (HR, 0.321; 95% CI, 0.267-0.386; P < .001).

“This is a positive study [that was done] in a very difficult setting to develop drugs: the refractory mCRC setting,” said Dasari, who is an associate professor in the Department of Gastrointestinal Medical Oncology, of the Division of Cancer Medicine, at the University of Texas MD Anderson Cancer Center. “[Fruquintinib] showed clinically meaningful benefits in terms of OS and PFS, with a favorable toxicity profile.”

In an interview with OncLive®, Dasari discussed the results of the phase 3 FRESCO-2 trial of fruquintinib in patients with refractory mCRC, the significance of the data for the treatment paradigm, and the potential next steps for examining the agent in this disease.

OncLive®: What was the rationale for investigating fruquintinib in patients with mCRC as part of the FRESCO-2 trial?

Dasari: CRC, unfortunately, continues to be one of the leading causes of cancer mortality. Treatment options in the refractory setting are very limited, and this is a huge unmet need. [FRESCO-2] was designed to address that huge unmet need for these patients.

What did the patient population look like for this trial?

These were patients with mCRC who had progressed on all available therapies. To be more specific, [patients progressed on] all the available conventional cytotoxic chemotherapy; targeted therapies, as appropriate; and trifluridine/tipiracil [TAS-102; Lonsurf] or regorafenib [Stivarga]—the other 2 oral agents that are available in this heavily pretreated setting.

Please expand on the study design and its key objectives.

This was a global, randomized, placebo-controlled, phase 3 trial. [Eligible] patients were [randomly assigned] 2:1 to fruquintinib dosed at 5 mg daily for 3-weeks-on/1-week-off schedule, [vs placebo]. Both arms also received best supportive care.

The primary end point of the trial was OS, and a key secondary end point was PFS. Other secondary end points included objective response rate, disease control rate, and safety.

What efficacy results were shared at the 2022 ESMO Congress?

We are excited about these results. The study was positive and met its primary [OS] end point, with a hazard ratio of 0.66, [translating to] a 34% reduction in the risk of death for patients treated with fruquintinib compared with placebo. This was a huge result for both patients and providers in this setting.

PFS was a key secondary end point, and there was an improvement in PFS with a hazard ratio of 0.321; this is a statistically and clinically significant result.

Not only was the drug effective, but it was also well tolerated with a favorable safety profile; this is very important for patients who have a huge tumor burden and several ongoing symptoms. [These findings] support the consideration of this drug as a new treatment option for patients with metastatic CRC.

Please expand on the safety data reported with the agent in this population.

Grade 3 or higher toxicities that are commonly noted in other VEGF TKIs [include] hand-foot syndrome, proteinuria, and other toxicities. [However, these] were not common with [fruquintinib]. These toxicities were seen in less than 7% of patients.

Overall, there was a good, favorable toxicity profile. The rates of discontinuation in the treatment and the placebo arms were [similar at 20.4% in the fruquintinib arm and 21.3% in the placebo arm].

What is the clinical significance of these data, and what do they mean for the treatment paradigm overall?

Overall, the study data suggest that this drug is effective through the continuum of care, especially when combining these data with [those from] the original [phase 3] FRESCO trial [NCT02314819] that was done in China. [In FRESCO], patients were less heavily pretreated compared with [those in FRESCO-2], but we saw similar benefits in terms of OS and a similar favorable toxicity profile. Overall, it seems that [fruquintinib] fits well into multiple settings across the treatment continuum.

The study was designed in partnership with a global regulatory agency. The sponsor is in communication with all these agencies and hoping for a favorable regulatory review so that this drug could be available for patients around the globe.

Please expand on the next steps for fruquintinib.

In the short term, it is hoped that this will be a new treatment option for patients globally. Building on these results, we also are hoping that we can design and conduct future trials. For instance, we have ongoing trials evaluating combination [regimens] with fruquintinib, specifically fruquintinib plus immunotherapy.

There are also more trials combining fruquintinib with other drugs in later-line [settings], and some are also looking to move fruquintinib into earlier lines of therapy for [patients with] CRC.


Dasari NA, Lonardi S, Garcia-Carbonero R, et al. FRESCO-2: a global phase 3 multiregional clinical trial evaluating the efficacy and safety of fruquintinib in patients with refractory metastatic colorectal cancer. Ann Oncol. 2022;33(suppl 7):S1391-S1392. doi:10.1016/annonc/j.annonc.2022.08.021

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