Updated data from a phase 2 study presented at the 2025 ASCO Gastrointestinal Cancers Symposium reveals that the combination of fruquintinib (Fruzaqla) and trifluridine/tipiracil (TAS-102; Lonsurf) demonstrates promising clinical activity and manageable toxicity in patients with previously treated metastatic colorectal cancer (mCRC). The study offers a potential new therapeutic avenue for patients who have exhausted other treatment options.
The phase 2 trial (NCT05004831) enrolled 50 patients with metastatic or recurrent CRC who had received at least two prior lines of therapy. Patients received fruquintinib at 4 mg once daily on days 1 to 21 combined with TAS-102 at 35 mg/m² twice daily on days 1 to 5 and 8 to 12 of every 4-week cycle. The primary endpoint was progression-free survival (PFS), with secondary endpoints including objective response rate, disease control rate, overall survival (OS), and safety/tolerability.
Efficacy Outcomes
The combination therapy yielded a median PFS of 6.33 months (95% CI, 4.20-8.62). The 6-, 9-, and 12-month PFS rates were 53.0% (95% CI, 40.2%-70.0%), 28.3% (95% CI, 17.4%-45.9%), and 23.1% (95% CI, 13.2%-40.5%), respectively. At a median follow-up of 17.6 months, the median OS was 18.4 months (95% CI, 12.0-NA), with 6-, 9-, and 12-month OS rates of 87.0% (95% CI, 77.8%-97.3%), 66.9% (95% CI, 54.0%-82.9%), and 64.3% (95% CI, 51.1%-80.8%), respectively.
According to lead study investigator Jianjun Peng, MD, PhD, a gastrointestinal surgeon at The First Affiliated Hospital, Sun Yat-sen University in Guangzhou, China, "The updated analysis demonstrated encouraging survival benefits of fruquintinib plus TAS-102 as third-line treatment in patients with mCRC with acceptable toxicities. This regimen could be an alternative therapeutic approach for these patients."
Safety Profile
Treatment-related adverse events (TRAEs) were primarily hematologic and consistent with the known safety profiles of fruquintinib and TAS-102. The most common any-grade TRAEs reported in at least 10% of patients included decreased neutrophil count (80%), decreased white blood cell count (70%), anemia (58%), proteinuria (50%), and decreased platelet count (44%).
Trial Design and Patient Characteristics
The study enrolled patients aged 18 to 75 years with metastatic or recurrent CRC who had previously received at least two treatment regimens and had not been exposed to prior anti-VEGF therapy. The median age of the cohort was 60 years (range, 39-76), and 58.0% of the patients were male. Patients had received a median of 2 prior lines of therapy (range, 1-4). All patients had received prior 5-fluorouracil, and most had also received irinotecan (90.0%) and oxaliplatin (98.0%).
Implications for mCRC Treatment
These findings suggest that the combination of fruquintinib and trifluridine/tipiracil may offer a valuable treatment option for patients with heavily pretreated mCRC, addressing a significant unmet need in this patient population. Further research, including larger randomized controlled trials, is warranted to confirm these results and further define the role of this combination in the mCRC treatment landscape.
