Time to grade ≥3 adverse events in pts receiving trifluridine/tipiracil (TAS-102).

788 Background: The phase 3 RECOURSE showed that treatment with trifluridine/tipiracil in patients (pts) with refractory metastatic colorectal cancer was associated with significantly improved survival versus placebo (7.1 versus 5.3 months, respectively; HR for death 0.68, 95% CI 0.58–0.81, p < 0.001), with few serious adverse events. Trifluridine/tipiracil is administered in 4-week cycles comprising 2 weeks with 5 days at 35 mg/m2 bid followed by 2 rest days, and then a 2-week rest period. Exploration of timing for AEs, particularly within the first cycle of treatment, is important for pt monitoring in the outpatient setting. Methods: We performed a post hoc analysis of the RECOURSE safety population (533 trifluridine/tipiracil; 265 placebo) to explore timing of hematological and nonhematological AEs. Results: Grade ≥ 3 adverse events (AEs) were more frequent with trifluridine/tipiracil than placebo for both hematological AEs (38% vs 0% neutropenia; 4% vs 0% febrile neutropenia; 18% vs 3% anemia; and 5% vs < 1% thrombocytopenia) and nonhematological AEs (2% vs 1% nausea; 2% vs < 1% vomiting; and 3% vs < 1% diarrhea). The median time to nadir in cycle 1 for hematological events was 28 days (17–31) for grade ≥ 3 neutropenia, 22 days (9–39) for grade ≥ 3 anemia, and 18 days (9–33) for grade ≥ 3 thrombocytopenia; similar values were obtained in subsequent cycles. The median times to nadir and values at nadir over the whole treatment duration (all cycles) are presented in the table for hematological and nonhematological AEs. Conclusions: Hematological and nonhematological AEs with trifluridine/tipiracil appear to be most intense towards the end of treatment cycles, which is reassuring for its use in the outpatient setting. Clinical trial information: NCT01607957. [Table: see text]