Trifluridine/Tipiracil Plus Bevacizumab Escalation Demonstrates Promise Among Patients With Advanced or Unresectable Metastatic Colorectal Cancer
According to results from the phase 2 E-BiTS study, intrapatient escalation of biweekly trifluridine/tipiracil plus bevacizumab demonstrated promising efficacy and safety among patients with advanced or unresectable metastatic colorectal cancer (mCRC).
“Trifluridine/tipiracil plus bevacizumab remains a standard of care for refractory [mCRC], though hematological toxicities remain a concern,” stated Munehiro Wakabayash, MD, Aichi Cancer Center Hospital, Nagoya, Japan, and coauthors. “Although a biweekly regimen has shown favorable tolerability, the optimal biweekly dosage has yet to be established.”
In this open-label, single-arm study, 34 patients received 35 mg/m2 of twice daily trifluridine/tipiracil once every 2 weeks (on days 1 to 5 of each cycle) plus 5 mg/kg of bevacizumab (on day 1 of each cycle) until disease progression or unacceptable toxicity. Escalation of 10 mg per day per cycle (up to a maximum of 30 mg/day) was permitted during cycles 2 to 4 based on tolerability. The primary end point was disease control rate. Key secondary end points included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), relative dose intensity, and safety.
At a median follow-up of 18 months, the disease control rate was 72.7%. Median PFS was 5.6 months, median OS was 17.6 months, and the ORR was 9.1%. Any-grade neutropenia was reported in 74% of patients in the overall population and in 61% of patients eligible for trifluridine/tipiracil dose escalation. Efficacy outcomes were significantly improved in patients who experienced grade ≥ 2 neutropenia. No patients discontinued treatment due to adverse events during the dose-escalation phase. Serious treatment-related adverse events of colonic perforation, kidney infection, and upper gastrointestinal hemorrhage each occurred in 1 patient. No treatment-related deaths occurred.
“Intrapatient dose escalation of biweekly [Trifluridine/tipiracil plus bevacizumab] was feasible and well tolerated and may enhance the efficacy of refractory mCRC treatment,” concluded Dr Wakabayash et al. “Nonetheless, further studies are warranted to validate this individualized dosing strategy.”
Source:
Wakabayaski M, Taniguchi H, Makiyama A, et al. A phase II study of intrapatient dose escalation of biweekly trifluridine/tipiracil plus bevacizumab for colorectal cancer (E-BiTS study). ESMO Open. Published online: August 29, 2025. doi: 10.1016/j.esmoop.2025.105571
