On 2 August 2023, the US Food and Drug Administration (FDA) approved trifluridine and tipiracil (LONSURF, Taiho Oncology, Inc.) with bevacizumab, for metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. FDA had previously approved single-agent LONSURF for this indication in September 2015.
Full prescribing information for LONSURF is available here.
Safety and efficacy were evaluated in SUNLIGHT (NCT04737187), a randomised, open-label, multicentre, global study of LONSURF with bevacizumab compared to single-agent LONSURF in 492 patients with mCRC who received a maximum of two prior chemotherapy regimens and demonstrated progressive disease or intolerance to the last regimen.
The primary efficacy outcome measures were overall survival (OS) and progression-free survival (PFS). The study demonstrated a statistically significant OS improvement in patients randomised to the LONSURF plus bevacizumab arm compared to those randomised to LONSURF (hazard ratio [HR] 0.61; 95% confidence interval [CI] 0.49, 0.77; 1-sided p < 0.001). Median OS was 10.8 months in the LONSURF plus bevacizumab arm (95% CI 9.4, 11.8) and 7.5 months in the LONSURF arm (95% CI 6.3, 8.6). Median PFS was 5.6 months in the LONSURF plus bevacizumab arm (95% CI 4.5, 5.9) and 2.4 months in the LONSURF arm (95% CI 2.1, 3.2), (HR 0.44; 95% CI 0.36, 0.54; 1-sided p < 0.001).
The most common adverse reactions or laboratory abnormalities for LONSURF with bevacizumab (≥ 20%) are neutropenia, anaemia, thrombocytopenia, fatigue, nausea, increased AST, increased ALT, increased alkaline phosphatase, decreased sodium, diarrhoea, abdominal pain, and decreased appetite.
The recommended LONSURF dose is 35 mg/m2 orally twice daily with food on days 1 through 5 and days 8 through 12 of each 28-day cycle. Refer to the Prescribing Information for bevacizumab dosing information.
This application was granted priority review designation.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Center of Excellence Project Facilitate.
