FDA Approves Trifluridine/Tipiracil With Bevacizumab For Metastatic Colorectal Cancer

FDA Approves Trifluridine/Tipiracil With Bevacizumab For Metastatic Colorectal Cancer

The FDA approved trifluridine and tipiracil (Lonsurf) plus bevacizumab as a treatment for patients with metastatic colorectal cancer (mCRC) who have already received treatment with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and—for those with RAS wild-type disease—an anti-EGFR therapy.

Of note, trifluridine and tipiracil, without bevacizumab, was approved for patients with metastatic colorectal cancer in September 2015. The decision to support the agent with bevacizumab is supported by findings from the phase 3 SUNLIGHT trial (NCT04737187), which demonstrated that the triple regimen induced a statistically significant overall survival (OS) rate.

Patients who received the triplet combination achieved a median OS of 10.8 months (95% CI, 9.4-11.8), whereas those receiving trifluridine/tiripacil alone achieved a median OS of 7.5 months (95% CI, 6.3-8.6). The hazard ratio for OS was 0.6 (95% CI, 0.49-0.77; 1-sided P < .001).¹ At 6 months, the OS rates between the 2 arms were 77% vs 61%, respectively, and at 12 months, the rates were 43% vs 30%.²

Progression-free survival (PFS) was also improved among those who received the triplet (HR, 0.44; 95% CI, 0.36-0.54; 1-sided P < .001).¹ The median PFS was 5.6 months (95% CI, 9.4-11.8) with bevacizumab and 7.5 months (95% CI, 6.3-8.6) without bevacizumab. The 6-month PFS rates were 43% vs 16%, respectively, and the 12-month rates were 16% vs 1%.²

The SUNLIGHT study enrolled a total of 492 heavily pretreated patients with mCRC. The median age of participants was 62 years (range, 20-84) and 64 years (range, 24-90) in the experimental and control arms, respectively. In either arm, 72% of patients had undergone prior treatment with bevacizumab.²

In the trial, patients experienced similar overall adverse event (AE) rates. The rate of severe AEs was 72% with the triplet and 70% with the doublet combination. In both arms, 13% of patients needed to withdraw from the study because of an AE.

The most common adverse events to occur in the experimental arm during the trial were neutropenia, anemia, thrombocytopenia, fatigue, nausea, increased AST, increased ALT, increased alkaline phosphatase, decreased sodium, diarrhea, abdominal pain, and decreased appetite.³

The prescribing label for the trifluridine/tiripacil lists severe myelosuppression and embryo-fetal toxicity under warnings and precautions. The label recommends that complete blood counts be obtained prior to and on day 15 of each treatment cycle.It also notes that trifluridine/tiripacil is not suitable among patients with baseline moderate or severe hepatic impairment and should not be initiated in these patients. If patients have severe renal impairment at baseline, they must receive a reduced dose of trifluridine/tiripacil.³

References

1. FDA approves trifluridine and tipiracil with bevacizumab for previously treated metastatic colorectal cancer. FDA. August 2, 2023. Accessed August 2, 2023. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-trifluridine-and-tipiracil-bevacizumab-previously-treated-metastatic-colorectal-cancer
2. Tabernero J, Prager GW, Fakih M, et al. Trifluridine/tipiracil plus bevacizumab for third-line treatment of refractory metastatic colorectal cancer: The phase 3 randomized SUNLIGHT study. J Clin Oncol. 2023;41(suppl 4):4. doi:10.1200/JCO.2023.41.3_suppl.4
3. Trifluridine/tipiracil (Lonsurf). Prescribing information. Taiho Oncology, Inc; August 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/207981s012lbl.pdf