In the treatment of metastatic colorectal cancer (mCRC), biweekly or 14-day dosing of trifluridine–tipiracil (FTD–TPI) plus bevacizumab is noninferior to the conventional 28-day dosing schedule, with similar survival outcomes but reduced haematological and gastrointestinal toxicity, according to the pragmatic phase III PRABITAS trial with broad eligibility criteria.
PRABITAS met its primary endpoint of overall survival (OS), reported Dr Hiroya Taniguchi at Aichi Cancer Center Hospital, Nagoya, Japan.
Over a median follow-up of 17.9 months, median OS was 11.3 months with biweekly dosing vs 10.3 months with conventional dosing (hazard ratio [HR], 0.93, 95 percent confidence interval [CI], 0.80–1.08; p<0.0001 for noninferiority), Taniguchi continued. [ESMO 2026, abstract LBA31]
“The curves overlapped at first and then separated in favour of the 14-day dosing schedule, but superiority was not shown,” he said.
Results were similar in an analysis that excluded patients who would have been excluded in explanatory randomized trials, including those with organ dysfunction, comorbidity, or ECOG PS of 2 (HR, 0.90, 95 percent CI, 0.76–1.05).
Progression-free survival was 3.9 months in both groups, objective response rates were 2 percent in both groups, and disease control rates were 52 percent in the 14-day group and 47 percent in the 28-day group. The 12-month OS rates were 47.5 percent and 44 percent, respectively.
In terms of safety, grade ≥3 haematological treatment-related adverse events (TRAEs) occurred less frequently in the 14-day vs 28-day group, including neutropenia (13 percent vs 39 percent), leukopenia (7 percent vs 18 percent), and febrile neutropenia (1 percent vs 5 percent).
Grade≥2 non-haematological TRAEs were also fewer in the 14-day vs 28-day group. These included anorexia (15 percent vs 26 percent), nausea (12 percent vs 18 percent), and diarrhoea (4 percent vs 10 percent). Two treatment-related deaths occurred in the 14-day group and none in the 28-day group.
“These findings support adoption of the 14-day FTD–TPI plus bevacizumab schedule as the preferred standard of care for refractory mCRC,” Taniguchi said.
The PRABITAS trial
The investigator-initiated PRABITAS trial was conducted across 178 sites in Japan and included 970 patients (median age 68 years, 57 percent male) with refractory mCRC. The trial adopted several pragmatic elements, including broad eligibility criteria, physician-directed dose modification, local tumour assessment, and streamlined data collection, all of which were aligned with routine clinical practice, as Taniguchi pointed out.
Patients were randomly allocated to the 14-day group (n=486) or the 28-day group (n=484). The 14-day group received oral FTD–TPI 35 mg/m2 twice daily on days 1–5 plus intravenous bevacizumab 5 mg/kg on day 1 of a 14-day cycle. The 28-day group received FTD–TPI on days 1–5 and 8–12 plus bevacizumab on days 1 and 15 of each 28-day cycle.
Overall, 59 percent of patients harboured RAS mutations, 99 percent received prior anti-VEGF agents, and 15 percent patients were prospectively classified as explanatory trial-ineligible (ie, ECOG PS 2, clinically significant organ dysfunction, or major comorbidities).
Compared with conventional dosing, biweekly dosing was associated with lower dose reductions (31 percent vs 48 percent), less frequent cycle delays (58 percent vs 68 percent), and higher median relative dose intensity (83 percent vs 77 percent).
“PRABITAS highlights the potential value of pragmatic investigator-initiated trials for addressing clinically important treatment-optimization questions that are unlikely to be prioritized through conventional drug-development pathways,” Taniguchi said.