Post Hoc Data Highlight Utility of Fruquintinib Across Metastatic Subgroups in Refractory mCRC

Rocío García-Carbonero, MD, PhD

The clinical benefit demonstrated by fruquintinib (Fruzaqla) across key subgroups defined by baseline metastatic sites in patients with refractory metastatic colorectal cancer (mCRC) highlights the applicability of the agent in this heavily pretreated setting, according to Rocío García-Carbonero, MD, PhD.

Findings from a prespecified, post hoc subgroup analysis of the phase 3 FRESCO-2 trial (NCT04322539) presented at the 2025 ESMO Gastrointestinal Cancers Congress showed improved overall survival (OS) with fruquintinib vs placebo in patients with liver-only metastases (HR, 0.256; 95% CI, 0.079-0.824; P = .0760), those with bone metastases with or without other metastatic sites (HR, 0.399; 95% CI, 0.215-0.741; P = .0065), and patients with peritoneal metastases with or without other metastatic sites (HR, 0.669; 95% CI, 0.395-1.134; P = .2453). In the lung-only subgroup, an OS benefit was not observed (HR, 0.998; 95% CI, 0.208-4.792; P = .9561), although the median OS reached 14.1 months with fruquintinib and was not evaluable for placebo due to immature data.

“I see this [agent] as one more opportunity for our patients,” García-Carbonero said. “It’s reasonably well tolerated. We know how to manage TKIs [tyrosine kinase inhibitors] by now—there are many TKIs used in the field—and it’s something oncologists are comfortable handling. This is good news for our patients.”

In an interview with OncLive®, García-Carbonero discussed the background of FRESCO-2, detailed findings from the post hoc analysis, and explained how these add to the body of evidence for fruquintinib in refractory mCRC.

García-Carbonero is a medical oncologist at the Hospital Universitario 12 de Octubre and an associate professor at Universidad Complutense of Madrid in Spain.

OncLive: What was the rationale behind the FRESCO-2 trial?

García-Carbonero: The FRESCO-2 study was a global trial conducted mainly in Western countries in patients with mCRC who had [progressed on] all standard therapies—meaning at least fluoropyrimidine, irinotecan, and oxaliplatin; bevacizumab [Avastin]; anti-EGFR [agents] if RAS and BRAF wild-type; and [at least 1 of] trifluridine/tipiracil [Lonsurf] or regorafenib [Stivarga].

This was conducted in a setting with no alternative options for care. CRC is one of the most prevalent cancers we have, and even in the fourth-line setting and beyond, there are still many patients who are very fit, but for whom we don’t have treatment options. This [represents] a highly unmet medical need.

What was the design of the FRESCO-2 trial and this subgroup analysis?

This trial was a randomized, double-blind, placebo-controlled trial, [with patients randomly assigned] 2:1 to receive fruquintinib or placebo.

The trial enrolled [691] patients and demonstrated a significant improvement in progression-free survival [PFS] and OS [in the intention-to-treat population] in a meaningful way. A 3-month improvement in this setting is fairly good.

The subgroup analysis explored the benefit of fruquintinib based on the localization of metastatic disease. We analyzed 4 subgroups: patients with liver-only metastases, patients with lung-only metastases, patients with bone metastases [with or without other sites], and patients with peritoneal disease [with or without disease in other metastatic sites].

These subgroups are not very large—liver-only and lung-only each made up approximately 4% to 5% of the patient population. The bone metastases subgroup accounted for approximately 11%, and the peritoneal disease subgroup was approximately 15%.

What efficacy results were observed in this analysis?

We saw that fruquintinib improves OS across all of these subgroups. However, these differences appear to be more prognostic than predictive, as fruquintinib improved OS vs placebo within each subgroup. The only subgroup in which we couldn’t demonstrate statistical significance was the lung-only group, but this was due to the unexpectedly favorable outcomes [in the placebo arm]. The median OS for fruquintinib-treated patients in this subgroup was 14.1 months, and we didn’t have enough events to demonstrate a statistically significant benefit. Still, we observed improved disease control rates and PFS across all subgroups.

[Although] certain sites of metastases are associated with poorer prognosis, all appear to derive clinical benefit from fruquintinib.

How do these findings add to previous data for fruquintinib in refractory mCRC?

[Fruquintinib] represents one more option in the continuum of care for these patients. It is always a positive development, as each option adds value. The CRC field is a good example of how small, incremental gains across lines of therapy can ultimately lead to meaningful overall improvements. Each treatment line may add 2 to 3 months [of survival], but in the end, [they allow more patients to live longer], and there is a subset of patients who can benefit for an extended period.

Reference

García-Carbonero R, Dasari A, Eng C, et al. Efficacy and safety of fruquintinib vs placebo by metastatic site in metastatic colorectal cancer: a FRESCO-2 subgroup analysis. Presented at: 2025 ESMO Gastrointestinal Cancers Congress; July 2-5, 2025; Barcelona, Spain. Abstract 37P.