FDA Gives Priority Review to Trifluridine/Tipiracil in Metastatic CRC

The FDA has accepted and granted priority review to a supplemental new drug application (sNDA) for trifluridine/tipiracil (Lonsurf) alone or in combination with bevacizumab (Avastin) for adult patients who have received prior treatment for metastatic colorectal cancer (CRC), according to a press release from Taiho Oncology, Inc.¹

Findings from the phase 3 SUNLIGHT study indicated that trifluridine/tipiracil plus bevacizumab had a manageable safety profile in the treatment of patients with metastatic CRC.

Findings from the phase 3 SUNLIGHT study (NCT04737187), which investigators presented at the 2023 Gastrointestinal Cancers Symposium, supported the sNDA for this regimen. The median overall survival (OS) was 10.8 months for patients receiving trifluridine/tipiracil plus bevacizumab vs 7.5 months in the trifluridine/tipiracil alone group (hazard ratio [HR], 0.61; 95% CI, 0.49-0.77; P <.001).² Additionally, the 6-month and 12-month OS rates in each respective group were 77% vs 61% and 43% vs 30%.

The median progression-free survival (PFS) in the trifluridine/tipiracil plus bevacizumab group was 5.6 months, and the median PFS in the trifluridine/tipiracil alone group was 2.4 months (HR, 0.44; 95% CI, 0.36-0.54; P <.001). The 6-month and 12-month PFS rates in each respective group were 43% vs 16% and 16% vs 1%.

“The poor prognosis for patients with previously treated, late-stage metastatic [CRC] has been an ongoing challenge in the oncology community, which has driven our pursuit of a potential new treatment option,” Volker Wacheck, MD, PhD, vice president of Clinical Development at Taiho Oncology, said in the press release. “We believe the combination of trifluridine/tipiracil plus bevacizumab may represent a significant advance in the treatment of refractory disease, and we look forward to working with the FDA as it considers this application.”

Investigators of the multinational, active-controlled, open-label, randomized phase 3 SUNLIGHT trial compared the safety and efficacy of trifluridine/tipiracil plus bevacizumab with trifluridine/tipiracil alone in those with refractory metastatic CRC following 2 chemotherapy regimens.

A total of 492 patients were randomly assigned 1:1 to receive 35 mg/m2 of trifluridine/tipiracil orally twice a day on days 1 to 5 and days 8 to 12 every 28 days on its own (n = 246) or in combination with 5 mg/kg of bevacizumab intravenously on days 1 and 15 every 28 days (n = 246).

The primary end point of the SUNLIGHT study was OS. Secondary end points included PFS, disease control rate, objective response rate, and safety.

Those who received at least 2 prior treatment regimens for histologically confirmed metastatic CRC were eligible for enrollment on the trial. Patients were also able to enroll if they had disease progression or intolerance, known RAS status, and an ECOG performance status of 0 or 1.

Most patients in the trifluridine/tipiracil plus bevacizumab and trifluridine/tipiracil alone arms, respectively, were male (50% vs 55%), from Europe (64% vs 64%), had primary tumor localization in the left colon (75% vs 69%), and were RAS mutant (70% vs 69%). Additionally, most patients in both groups had received prior therapy with an anti-VEGF agent (76% vs 76%) and bevacizumab (72% vs 72%).

The most frequent grade 3 or 4 treatment-emergent adverse effects observed in the trifluridine/tipiracil plus bevacizumab and trifluridine/tipiracil alone arms, respectively, included neutropenia (43.1% vs 32.1%) and anemia (6.1% vs 11.0%).

Investigators concluded that trifluridine/tipiracil plus bevacizumab demonstrated a manageable safety profile.

References

1. U.S. Food and Drug Administration accepts for priority review Taiho Oncology's supplemental new drug application for the use of trifluridine/tipiracil (LONSURF®) in combination with bevacizumab for refractory metastatic colorectal cancer (mCRC). News release. Taiho Oncology, Inc. April 18, 2023. Accessed April 18, 2023. prn.to/43FfazH
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):abstr 4. doi:10.1200/JCO.2023.41.4_suppl.4