Trifluridine/Tipiracil Plus Bevacizumab For Refractory Metastatic Colorectal Cancer

An Analysis of the Phase 3 SUNLIGHT Trial

At the 2023 World Congress on Gastrointestinal Cancers, Gerald Prager, MD, Medical University of Vienna, Austria, presents data from the SUNLIGHT trial, evaluating trifluridine/tipiracil plus bevacizumab for patients with refractory metastatic colorectal cancer.

Dr Prager concluded, "It's a very clear, straightforward study showing that in the third-line setting, trifluridine/tipiracil plus bevacizumab is a new standard of care treatment and this might affect also subsequent treatment options."

Transcript:

Hello. My name is Gerald Prager. I'm a medical oncologist specialized on GI cancer, working at the Medical University in Vienna, Austria. Today, I would like to give you an insight in the clinical phase 3 study called the SUNLIGHT study.

In this prospective randomized phase 3 trial, patients with metastatic colorectal cancer, who had been pretreated with 2 lines of treatment were either treated with trifluridine/tipiracil in the control arm, or with trifluridine/tipiracil plus bevacizumab. Patients with very good or good performance status could be included and the patients all had to be pretreated with oxaliplatin, irinotecan, fluoropyrimidines, bevacizumab. In case of RAS wild-type status, anti-GF receptor antibody. The primary end point of this study was overall survival. It was clearly a third-line treatment design so at maximum 2 prior lines of treatments were allowed. We could demonstrate that by the addition of bevacizumab, trifluridine/tipiracil was significantly superior when compared to the active treatment trifluridine/tipiracil alone. With an hazard ratio of 0.61, we could demonstrate a statistically significant benefit in favor of the combination with the anti-VEGF antibody.

The predefined subgroups of patients all had a benefit by adding bevacizumab to the oral anti-metabolic drug trifluridine/tipiracil. So it was independent of the RAS mutational status, independent whether patients were pretreated with bevacizumab or not, independent of the sided-ness of the primary tumor or ECOG performance status 0/1 or age.

A very good co-finding and secondary endpoint was that the time to deterioration of the performance status was delayed by the active treatment combination, which was also statistically significant. This means that patients treated with trifluridine/tipiracil plus bevacizumab were longer in a very good or good performance status and, therefore, potentially were more active to be treated in a subsequent line of treatment when eventually trifluridine/tipiracil bevacizumab fails.

It's important to mention this is demonstrated here at the ESMO GI meeting in Barcelona that the quality of life data were assessed. We will demonstrate that the quality of life is, although in the chemo combination with bevacizumab not impaired, and the patient, as I've mentioned before, stay longer on the active treatment and maintain the performance status and as well the quality of life.

Other secondary endpoint like progression-free survival or response rate were also statistically significantly higher when trifluridine/tipiracil was combined with the anti-VEGF antibody.

In summary, it's a very clear, straightforward study showing that in the third-line setting, trifluridine/tipiracil plus bevacizumab is a new standard of care treatment and this might affect also subsequent treatment options. As soon as there will be the availability of this drug combination, I think we should consider these treatment options for all our patients suffering for metastatic colorectal cancer and treated before with IV chemotherapy options.

With this, I want to thank you very much for your attention and have a good day.

Source:

Prager G, Taieb J, Fakih M, et al. Health-related quality of life associated with trifluridine/tipiracil in combination with bevacizumab in refractory metastatic colorectal cancer: An analysis of the phase 3 SUNLIGHT trial. Presented at the 2023 World Congress on Gastrointestinal Cancers; June 28-July 1, 2023; Barcelona, Spain. Abstract O-9