Biweekly dosing of trifluridine-tipiracil reduces rates of myelosuppression while maintaining efficacy in patients with metastatic colorectal cancer.

backgroundTrifluridine-tipiracil (TAS-102) is approved as monotherapy and in combination with bevacizumab for refractory unresectable metastatic colorectal cancer (mCRC). The recommended dose is 35 mg/m2 twice daily on days 1-5 and days 8-12 of 28-day cycles commonly resulting in grade 3-4 neutropenia, dose delays/reductions, and requiring GCSF support. To maintain efficacy and reduce toxicity, we analyzed a biweekly dosing schedule (days 1-5 and days 15-19 q28 days). PATIENTS AND

methodsA retrospective analysis was performed in patients with mCRC and appendiceal cancer who completed >12 days of TAS-102 therapy and underwent surveillance imaging every 8-12 weeks. ECOG performance status (PS), prior lines of therapy, use of bevacizumab, CTCAE grade of treatment-related myelotoxicity, dose reductions/delays, and use of GCSF were assessed. Among patients with mCRC, survival analyses were performed.

results61 patients met inclusion criteria, with mCRC:appendiceal CA ratio of 56:5. Median ECOG PS = 1; median number of prior therapies = 3; Reduction in grade ≥3 neutropenia (16.3%, 1 patient with grade 4) and grade ≥3 anemia (8.2%) relative to the historic controls of the RECOURSE and SUNLIGHT trials. No neutropenic fever was noted; GCSF was not required. Eight patients required a dose delay. In the mCRC patients, the median progression-free survival (PFS) was 4.2 months, with a median overall survival (OS) of 9.2 months.

conclusionsBiweekly dosing of TAS-102 demonstrated a reduction in myelosuppression, with similar PFS and OS. With an improved toxicity profile, this alternative dosing schedule may potentially broaden the utilization of TAS-102 in patients with borderline PS and provide a favorable option for future combination studies.