TAS-102/Bevacizumab Combo Improves OS Over TAS-102 Alone in Refractory mCRC

Colorectal Cancer

The addition of bevacizumab (Avastin) to trifluridine/tipiracil (TAS-102; Lonsurf) resulted in a statistically significant improvement in overall survival (OS) over TAS-102 alone in patients with refractory metastatic colorectal cancer (mCRC) after 2 chemotherapy regimens, meeting the primary end point of the phase 3 SUNLIGHT trial (NCT04737187).¹

Further data from the primary analysis of the trial will be shared at an upcoming international scientific conference, according to Servier, Taiho Oncology, Inc. and Taiho Pharmaceutical Company, Ltd.

“Findings from the SUNLIGHT trial could potentially represent a significant advancement in the treatment of patients with mCRC who have progressed after 2 lines of standard chemotherapy,” Nadia Caussé-Amellal, MD, head of Global Development, GI Indications, Oncology and Immuno-Oncology Therapeutic Area at Servier, stated in a press release. “Combining trifluridine/tipiracil with bevacizumab demonstrated the potential to extend survival in these patients who have limited therapeutic options.”

TAS-102 is an oral, active formulation of trifluridine, which is a thymidine-based nucleoside analog, and tipiracil hydrochloride, which is a thymidine phosphorylase inhibitor that boosts the bioavailability of trifluridine.2 Data from preliminary studies showed that the addition of bevacizumab to TAS-102 resulted in encouraging activity of patients with refractory mCRC.

In the multicenter, open-label, active-controlled, 2-arm phase 3 trial, investigators sought to further evaluate the safety and efficacy of the combination vs TAS-102 alone as a third-line treatment for these patients.

To be eligible for enrollment, patients were required to be at least 18 years of age, have histologically confirmed unresectable mCRC, have previously received at least 2 chemotherapy regimens for metastatic disease, and have progressed or become intolerant to their last regimen. Previous regimens must have comprised a fluoropyrimidine, irinotecan, oxaliplatin, and an anti-VEGF monoclonal antibody; in those with RAS wild-type disease, they must have received an EGFR monoclonal antibody.

They also needed to have a known RAS mutation, an estimated life expectancy of at least 12 weeks, an ECOG performance status of 0 or 1, and acceptable bone marrow, renal, hepatic, and coagulation function.

If they received more than 2 prior chemotherapy regimens for metastatic disease, or with TAS-102, had an unresolved grade 3 or higher non-hematologic toxicity linked with a prior chemotherapy regimen, central nervous system metastases that were unstable or required increasing doses of steroids for control, or underwent major surgery within 4 weeks prior to randomization, they were excluded.

A total of 492 participants were randomly assigned 1:1 to receive TAS-102 at 35 mg/m2 twice daily on days 1 through 5 and 8 through 12 every 28 days plus bevacizumab at 5 mg/kg on days 1 and 15 every 28 days or TAS-102 alone.

Stratification factors included geographic region (North America vs European Union vs the rest of the world), time since diagnosis of metastatic disease (less than 18 months vs 18 months or more), and RAS mutational status (wild-type vs mutant).

The primary objective of the research was to demonstrate the superiority of TAS-102 plus bevacizumab over TAS-102 alone with regard to OS. Important secondary end points included progression-free survival, overall response rate, disease control rate, quality of life, safety, and tolerability.

“Trifluridine/tipiracil – discovered by Taiho and developed in our partnership with Servier with the cooperation of many patients and healthcare professionals – has had a significant impact on the management of CRC for thousands of patients,” Fabio Benedetti, MD, global chief medical officer for Oncology at Taiho Pharmaceutical, added in the press release. “The results of this study may represent another advancement in the management of this disease, and we now look forward to the further analysis of secondary end points.”

References

1. Drug combination meets survival end point in phase III pivotal trial involving participants with refractory metastatic colorectal cancer. News release. Servier, Taiho Oncology, Inc. and Taiho Pharmaceutical Co., Ltd. September 12, 2022. Accessed September 13, 2022. https://bwnews.pr/3BArSnw
2. Tabernero J, Taieb J, Prager GW, et al. Trifluridine/tipiracil plus bevacizumab for third-line management of metastatic colorectal cancer: SUNLIGHT study design. Future Oncol. 2021;17(16):1977-1985. doi:10.2217/fon-2020-1238