FDA Approves Lonsurf Plus Avastin for Metastatic Colorectal Cancer

The Food and Drug Administration (FDA) has approved Lonsurf (trifluridine and tipiracil) plus Avastin (bevacizumab) for treatment of 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.

The approval, following a priority review designation of its application by the FDA, is based on findings from the phase 3 SUNLIGHT trial comparing Lonsurf and Avastin with single-agent Lonsurf, a treatment approved by the FDA in 2015.

The SUNLIGHT trial launched in November 2020, according to its listing on clinicaltrials.gov.

Among 492 participating patients with metastatic colorectal cancer who, according to the FDA, “received a maximum of two prior chemotherapy regimens and demonstrated progressive disease or intolerance to the last regimen,” median overall survival (the time following treatment until death of any cause) was 10.8 months for patients who received the combination therapy and 7.5 months for those treated with just Lonsurf.

The median progression-free survival (the time patients live without the disease spreading or worsening) was 5.6 months for patients treated with the combination therapy and 2.4 months for patients treated with single-agent Lonsurf.

According to the FDA, the most common side effects and/or laboratory abnormalities for patients treated with Lonsurf and Avastin were neutropenia (low white blood cells), anemia (low red blood cells), thrombocytopenia (low platelets), fatigue, nausea, increased AST, ALT and alkaline phosphatase (values indicative of liver damage), decreased sodium, diarrhea, abdominal pain and decreased appetite.

Findings from the SUNLIGHT study were published earlier this year in the New England Journal of Medicine.

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 at the time: “(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.

It was reported in May that patients treated with the combination therapy went an average of 9.3 months until experiencing a change in their performance status (an observable difference in the amount of independence or difficulty they had when performing daily tasks), compared with 6.3 months for patients in the single-agent group.

"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 earlier this year.

Lonsurf was also approved by the FDA in 2019 for the treatment of patients with previously treated metastatic gastric or gastroesophageal junction adenocarcinoma.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.