Lonsurf Plus Avastin May Fill a ‘Growing Need’ in Metastatic CRC

The two-drug combination of Lonsurf (trifluridine/tipiracil) plus Avastin (bevacizumab) improved survival outcomes in patients with metastatic colorectal cancer whose disease progressed on prior therapies, according to findings from the phase 3 SUNLIGHT study published in the New England Journal of Medicine.

Study findings showed that the drug duo resulted in lengthened progression-free survival (time from treatment until disease worsens) as well as overall survival (time from treatment until death of any cause) compared to Lonsurf alone in patients with refractory metastatic colorectal cancer who experienced disease progression or were intolerant to two prior chemotherapy regimens.

Lonsurf plus Avastin improved progression-free and overall survival in pretreated patients with metastatic colorectal cancer, findings from the SUNLIGHT trial showed.

The lead study author, Dr. Josep Tebernero, head of medical oncology at Vall d’Hebron University Hospital in Barcelona, Spain, summarized the promising prospect of these findings: “(Lonsurf) plus (Avastin) may represent a meaningful new treatment option in patients with (metastatic colorectal cancer) who have progressed after two lines of therapy,” he said in a statement from Taiho Oncology and Servier, the manufacturers of the agents.

The study included two groups (246 participants each) of patients with pretreated, metastatic, refractory colorectal cancer who were randomly assigned to receive either Lonsurf plus Avastin or Lonsurf alone.

Findings showed that the average overall survival was 10.8 months in the group that received the combination therapy, and 7.5 months in the Lonsurf-only group. Additionally, patients in the Lonsurf/Avastin group lived for an average of 5.6 months before their disease worsened, while patients in the Lonsurf group lived for an average of 2.4 months before their disease worsened.

The most common side effects observed in both groups were neutropenia (decrease in a type of white blood cell), nausea and anemia (decrease in red blood cells.) There were no treatment-related deaths reported in the study.

Of note, there was an average of 9.3 months and 6.3 months in the combination and single-agent groups, respectively, until patients experienced a change in their performance status, meaning that there was an observable difference in the amount of independence or difficulty in performing daily tasks.

"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," said Dr. Marwan Fakih, professor of medical oncology and therapeutics research, City of Hope, and lead U.S. investigator for the SUNLIGHT trial, said in the press release.

Based on these findings, the pharmaceutical companies submitted a supplemental New Drug Application (FDA) to the Food and Drug Administration. If approved, Taiho and Servier will be allowed to bring the combination of Lonsurf plus Avastin to the market for adults with metastatic colorectal cancer who were previously treated with luoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.

The FDA plans on making their approval decision by Aug. 13, 2023. Lonsurf was previously approved as a single agent (meaning that it was not given in combination with any other drugs) in September 2015 for patients with advanced colorectal cancer whose disease did not respond to other treatments. In 2019, the FDA approved Lonsurf for patients with previously treated metastatic gastric or gastroesophageal junction adenocarcinoma.

"The publication of the SUNLIGHT results in the New England Journal of Medicine speaks to the quality of the science and potential impact of this investigational combination on the treatment of metastatic colorectal cancer," Fakih said in the release.

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