Biweekly versus conventional trifluridine/tipiracil plus bevacizumab for refractory metastatic colorectal cancer: The pragmatic phase 3 PRABITAS trial

doi:10.1016/s0140-6736(26)01782-4

PRABITAS

Patient / Population Intervention / Exposition Vergleich Endpunkt

In patients with refractory metastatic colorectal cancer, biweekly trifluridine/tipiracil plus bevacizumab was non-inferior for overall survival compared with the conventional 28-day schedule, with less neutropenia.

N

972Patienten

Design

Pragmatic, investigator-initiated, open-label, randomised 1:1, phase 3 non-inferiority trial at sites in Japan, in patients with refractory metastatic colorectal cancer, comparing trifluridine/tipiracil plus bevacizumab on a biweekly schedule with the conventional 28-day schedule (jRCTs041230120).

Endpunkt

Overall survival in the intention-to-treat population, with a non-inferiority margin of 1.25 for the hazard ratio.

ErgebnisMedian overall survival 11.3 vs 10.3 months with the biweekly vs conventional schedule (stratified HR 0.93; 95% CI 0.80-1.08), meeting non-inferiority. Median PFS 3.9 vs 3.9 months (HR 0.93; 95% CI 0.81-1.06). In the 825 patients (85%) meeting standard eligibility criteria, OS HR 0.90 (95% CI 0.76-1.05). Grade ≥ 3 neutropenia 13% vs 39%, febrile neutropenia 1% vs 5%, G-CSF use 3% vs 13%, grade ≥ 2 anorexia 15% vs 26% and diarrhoea 4% vs 10%. Dose reductions 31% vs 48%, cycle delays 58% vs 68%, relative dose intensity 83% vs 77%.

Sakakida T, Taniguchi H, Asayama M, et al. The Lancet. 2026. 10.1016/s0140-6736(26)01782-4

Diskussion & Kritik

This large pragmatic trial shows that the biweekly schedule kept overall survival within the prespecified margin, since the upper confidence limit of 1.08 lies below 1.25, while clearly reducing neutropenia and gastrointestinal toxicity. The open-label design may bias toxicity reporting and treatment decisions, though the hard primary endpoint is less affected. The abstract gives no P value, number of deaths or quality-of-life data, and follow-up was reported only as a median of 17.9 months. All patients were treated in Japan, so generalisability to other populations is not addressed by the source.