Real-World Analysis Sheds Light on Fruquintinib Use in Later-Line Metastatic CRC

Findings from a real-world, prospective, non-interventional cohort study conducted in Portugal showed that fruquintinib (Fruzaqla) had a manageable safety profile and produced an efficacy trend in patients with refractory metastatic colorectal cancer (mCRC).¹

Data presented in a poster at the 2025 ESMO Gastrointestinal Cancers Congress demonstrated that evaluable patients treated with fruquintinib (n = 23) experienced 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).

In contrast, data from the phase 3 FRESCO-2 trial (NCT04322539) showed that patients with refractory mCRC treated with fruquintinib (n = 461) experienced a median OS of 7.4 months (95% CI, 6.7-8.2) compared with 4.8 months (95% CI, 4.0-5.8) for those given placebo (HR, 0.66; 95% CI, 0.55-0.80; P < .0001).² The median PFS was 3.7 months vs 1.8 months, respectively (HR, 0.32; 95% CI 0.27-0.39; P < .001).³

Lead study author, Dr Filipa R. Verdasca, and colleagues noted in the poster that the shorter OS and comparable PFS data between the real-world cohort and those given fruquintinib in FRESCO-2 could reflect broader comorbidities of a real-world population and differences in clinical practice. Verdasca is a member of the Department of Medical Oncology at Unidada Local de Saúde de São José in Lisbon, Portugal.

“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,” Verdasca and colleagues wrote in the poster. “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.”

In November 2023, the FDA approved fruquintinib for the treatment of adult patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy.⁴

In June 2024, the European Commission approved the agent for adult patients with mCRC who have been previously treated with available standard therapies, including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, anti-VEGF agents, and anti-EGFR agents, and who have progressed on or are intolerant to treatment with either TAS-102 or regorafenib (Stivarga).⁵

Both of these approvals were supported by data from FRESCO-2.

Diving into the Real-World Cohort Study

To evaluate real-world outcomes for fruquintinib in a European population, investigators of the multicenter, prospective, non-interventional cohort study enrolled patients with mCRC treated with fruquintinib between January 2024 and March 2025 at 1 of 5 Portuguese centers.¹

Medical records were used to pull clinical and demographic data, and the Kaplan-Meier method was used to calculate time-to-event outcomes.

The median age of the real-world population was 61 years (range, 55-68). The majority of patients were male (70%), had left-sided tumors (57%), and underwent primary tumor resection (87%). Patients had an ECOG performance status of 0 (30%), 1 (57%), or 2 (13%). Forty-three percent of patients had RAS, BRAF, and HER2 wild-type disease, and 48% harbored NRAS or KRAS mutations. BRAF mutations and HER2 mutations were reported in 1 patient each (4%). Notably, no patients had mismatch repair–deficient disease.

At baseline, patients had 1 metastatic site (35%), 2 metastases (13%), 3 metastases (30%), or at least 4 metastases (22%). Metastatic sites included liver (57%), lung (61%), lymph node (48%), peritoneal (26%), bone (17%), and central nervous system (22%). One patient (4%) received 2 lines of therapy prior to fruquintinib; the remainder of the population received 3 prior lines of therapy (61%), or at least 4 prior lines (35%).

Real-World Safety Findings

Any-grade treatment-related adverse effects (TRAEs) were reported in 73.9% of patients (n including 17.4% who experienced grade 3/4 TRAEs. In the safety evaluable population (n = 17), the most common grade 1/2 TRAEs included fatigue (n = 11), hypertension (n = 6), anemia (n = 4), diarrhea (n = 4), nausea/vomiting (n = 2), hemorrhage (n = 2), and mucositis (n = 1). Grade 3/4 TRAEs comprised hypertension (n = 3), mucositis (n = 1), and fatigue (n = 1).

Toxicity or intercurrent events led to treatment discontinuation in 39% of patients, and 30% of patients required dose reductions. The minimum dose received across the full population (n = 23) was 3 mg/m² (13%), 4 mg/mg² (26%), or 5 mg/mg² (61%).

Study authors noted that the rate of grade 3 or higher AEs occurred in 63% of patients treated with fruquintinib during FRESCO-2; however, the rates of treatment discontinuations (real-world, 39%; FRESCO-2, 20%) and dose reductions (30%; 24%) were higher in the cohort study, suggesting that greater clinical frailty and tolerability challenges in clinical practice may have influenced the increased rates.

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

References

1. Verdasca FR, Martins AP, Fernandes ACB, et al. Real-world data from fruquintinib in later line metastatic colorectal cancer. Presented at: 2025 ESMO Gastrointestinal Cancers Congress; July 2-5, 2025; Barcelona, Spain. Abstract 66P.
2. Dasari A, Lonardi S, Garcia-Carbonero R, et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO-2): an international, multicentre, randomised, double-blind, phase 3 study. Lancet. 2023;402(10395):41-53. doi:10.1016/S0140-6736(23)00772-9
3. HUTCHMED highlights phase III FRESCO-2 MRCT data summary of fruquintinib in refractory metastatic colorectal cancer from the upcoming ESMO 2022 presentation. News release. HUTCHMED. September 8, 2022. Accessed July 2, 2025. https://www.hutch-med.com/fruquintinib-fresco-2-data-summary-esmo-2022/
4. FDA approves fruquintinib in refractory metastatic colorectal cancer. FDA. November 8, 2023. Accessed July 2, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-fruquintinib-refractory-metastatic-colorectal-cancer
5. HUTCHMED announces European Commission approval for Fruzaqla (fruquintinib) received by Takeda. News release. HUTCHMED. June 21, 2024. Accessed July 2, 2025. https://www.hutch-med.com/european-commission-approval-for-fruzaqla-fruquintinib/