Fruquintinib Shows Promise for Refractory Colorectal Cancer

New findings suggest that fruquintinib (Fruzaqla) demonstrates a tolerable safety profile alongside encouraging efficacy for individuals battling metastatic colorectal cancer (mCRC) that has resisted other treatments. The research offers a beacon of hope in challenging cases.

Real-World Study in Portugal

A recent real-world study conducted in Portugal, presented at the 2025 ESMO Gastrointestinal Cancers Congress, assessed fruquintinib’s effectiveness. The study, led by **Dr. Filipa R. Verdasca** and colleagues, involved a cohort of patients with refractory mCRC.

The data revealed that patients treated with fruquintinib (n = 23) had a median overall survival (OS) of 4.0 months (95% CI, 0.47-7.53) and a median progression-free survival (PFS) of 3.0 months (95% CI, 0.96-5.04).

Comparison to FRESCO-2 Trial

The outcomes were then compared to the phase 3 FRESCO-2 trial. In that trial, patients with refractory mCRC treated with fruquintinib (n = 461) experienced a median OS of 7.4 months (95% CI, 6.7-8.2), versus 4.8 months (95% CI, 4.0-5.8) for those given a placebo.

The median PFS in the FRESCO-2 trial was 3.7 months compared to 1.8 months for the placebo group.

**Dr. Verdasca** and the research team noted that the differences in OS and PFS between the real-world cohort and the FRESCO-2 trial participants could be attributed to the broader range of health issues, or comorbidities, present in a real-world population, as well as differing clinical practices.

Insights from the Research Team

“To our knowledge, this is one of the first non-Asian, real-world datasets and one of the first analyzing sequencing results from trifluridine/tipiracil [TAS-102; Lonsurf] and bevacizumab [Avastin] followed by fruquintinib,” the authors wrote.

The team added, “Despite the small sample size and very short follow-up, we observed a manageable safety profile and an efficacy trend, despite modest outcomes, picturing a highly refractory disease setting and a possible role of previous treatments on VEGFR targeting.”

Regulatory Approvals

Fruquintinib received FDA approval in November 2023 for treating adult patients with mCRC who have previously undergone several lines of chemotherapy, anti-VEGF therapy, and, where appropriate, anti-EGFR therapy.

The European Commission followed suit in June 2024, approving fruquintinib for mCRC patients who have been pre-treated with standard therapies and have progressed on or are intolerant to TAS-102 or regorafenib.

According to the American Cancer Society, colorectal cancer is the third most common cancer diagnosed in both men and women in the United States, with an estimated 153,020 new cases in 2024 (American Cancer Society).

Study Details

The real-world study enrolled patients with mCRC treated with fruquintinib from January 2024 to March 2025 across five Portuguese centers. Researchers gathered clinical and demographic information from medical records, employing the Kaplan-Meier method to assess time-to-event outcomes.

The real-world population had a median age of 61 years. Most patients were male (70%) and had left-sided tumors (57%), with 87% undergoing primary tumor resection. ECOG performance statuses were 0 (30%), 1 (57%), or 2 (13%).

Genetic profiles showed that 43% of patients had RAS, BRAF, and HER2 wild-type disease, while 48% harbored NRAS or KRAS mutations.

Safety Profile

Treatment-related adverse effects (TRAEs) of any grade were observed in 73.9% of patients, including 17.4% experiencing grade 3/4 TRAEs. Common grade 1/2 TRAEs included fatigue, hypertension, anemia, diarrhea, nausea/vomiting, hemorrhage, and mucositis. Grade 3/4 TRAEs included hypertension, mucositis, and fatigue.

Due to toxicity or other events, 39% of patients discontinued treatment, and 30% required dose reductions.

The study authors pointed out that while the rate of grade 3 or higher adverse events was 63% in the FRESCO-2 trial, the real-world study saw higher rates of treatment discontinuations and dose reductions. This suggests real-world patients’ frailty and tolerability issues influenced these increased rates.

“We intend to broaden our accrual and increase follow-up time to evaluate safety and more mature outcomes,” the authors concluded.