Lonsurf Plus Avastin ‘Provides Extra Time’ for People With Advanced CRC

The Food and Drug Administration's (FDA) recent approval of Lonsurf (trifluridine and tipiracil) plus Avastin (bevacizumab) for patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, an anti-VEGF biological therapy and, if RAS wild-type, an anti-EGFR therapy has the potential to become a new standard of care, according to an expert.

“In the end, it provides extra time for people with advanced colorectal cancer whose main goal is quality of life and prolonging their time with their families and friends. It's an advancement for the field, and I think will become a new standard of care for patients looking for third line or fourth line treatment for advanced colon cancer,” Dr. Richard Goldberg, who served as West Virginia University Cancer Institute’s (WVUCI) director, said in an interview with CURE®.

Results from the SUNLIGHT trial showed that the median survival for patients who took Lonsurf combined with Avastin improved “by more than three months compared to those who just got Lonsurf alone,” explained Goldberg. The trial launched in 2020 and compared of Lonsurf and Avastin with single-agent Lonsurf, which was approved by the FDA in 2015.

“Lonsurf was approved as a single drug, although it's actually a combination of two drugs and one formulation, and it improved the median survival to about six months, which is what was shown in the control arm of the SUNLIGHT study,” Goldberg said.

SUNLIGHT, a randomized phase 3 trial, included 492 patients who had metastatic colorectal cancer. All patients received chemotherapy prior to the study and showed disease progression or intolerance to previous treatment. The median overall survival (time from treatment until death of any cause) was 7.5 months for Lonsurf alone and 10.8 months for the combination of Lonsurf plus Avastin. Progression-free survival (time from treatment initiation until disease progression or worsening) was 2.4 months and 5.6 months in the single-agent and combination groups, respectively.

Although the combination therapy improved outcomes, there are some side effects that come with the therapy.

“The main side effect it has is it lowers the body's infection-fighting power, so it causes what's called granulocytopenia or reduction in white blood cells. It seldom causes infection. Most of the time patients don't notice that. And then it can have some modest side effects like some mild nausea or some diarrhea,” said Goldberg. “You know, the combination of the two drugs is really no more toxic than the single drug alone.”

Lonsurf is taken in the form of a pill, while Avastin is in the form of an IV, so a clinic is necessary to receive the medication every other week. Since Lonsurf has been approved since 2015, doctors are aware of the main side effects and its accessibility.

"Individuals living with metastatic colorectal cancer and who have progressed following fluoropyrimidine, oxaliplatin, irinotecan, (Avastin) and anti-epidermal growth factor receptor (EGFR) antibodies — if RAS wild-type — have limited treatment options. There is a growing need for new approaches that improve survival in this population," Dr. Marwan Fakih, professor of medical oncology and therapeutics research, City of Hope, and lead U.S. investigator for the SUNLIGHT trial, said in a press release.

Although this combination is an advancement for this patient population, there remains an unmet need and this will require investment in future research until we find the right tools to cure all people with advanced colorectal cancer, according to Goldberg.

“One of the things that we're understanding is that colorectal cancer isn't just one disease, it's driven by a number of different mutations. And the main unmet needs for those patients to have better success is to unravel the differences and then target the differences specifically with new drugs,” explained Goldberg.

Investigating Lonsurf further with other medications can be impactful for patients with colorectal cancer in the future.

“Combinations of Lonsurf with other targeted therapies would seem to be a fruitful area for further research,” said Goldberg.

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