Combination drug approved in Europe for metastatic colorectal cancer

A new combination oral treatment, Lonsurf, has been granted a marketing authorisation for adults with metastatic colorectal cancer by the European Commission.

Lonsurf is a novel oral anticancer drug, combining trifluridine (FTD) and tipiracil (TPI), and is approved for patients who have been previously treated with — or are not considered candidates for — fluoropyrimidine-based, oxaliplatin-based and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents.

The EC’s decision on 25 April 2016 follows a positive opinion by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) in February 2016, which recommended approval of Lonsurf, based on data from the phase III RECOURSE study that showed significantly increased overall survival in patients who took the drug.

The RECOURSE study^[1]
compared Lonsurf with best supportive care (BSC) and placebo with BSC in 800 patients with previously treated metastatic colorectal cancer. The results showed that patients who took Lonsurf had a 31% relative reduction in the risk of death (HR=0.69; 95% confidence interval [CI]: 0.59–0.81; P<0.0001) and two months greater median overall survival compared with patients who received BSC alone. The median overall survival was 7.2 months for Lonsurf with BSC compared with 5.2 months for placebo with BSC, and the one-year survival rates were 27.1% and 16.6%, respectively.

Steve Williamson, consultant cancer pharmacist at Northumbria Healthcare NHS Trusts, says: “The availability of Lonsurf to patients in England with advanced colorectal cancer will depend on it being approved through the National Institute for Health and Care Excellence or the new Cancer Drug Fund process.

“The trial results show a two month improvement in overall survival. As the initial licence will be for last line therapy after other standard treatments have failed, the effect of Lonsurf on patients’ quality of life will be a key factor that commissioners will have to consider given its modest impact on survival.”

The most frequently observed side effects in patients receiving Lonsurf were neutropenia, nausea, decreased appetite, diarrhoea, fatigue, anaemia, thrombocytopenia, increase in total bilirubin, alkaline phosphatase and ASAT levels, and leucopenia.

Lonsurf is already available in Japan and the United States, where Taiho Pharmaceutical holds the marketing authorisation. Servier entered into an exclusive license agreement with Taiho in June 2016 for rights to co-develop and market it in Europe and other countries outside of the United States, Canada, Mexico and Asia.

Lonsurf’s trifluridine (FTD) and tipiracil (TPI) combination is designed to maintain clinical activity. FTD is an antineoplastic nucleoside analogue, which is incorporated directly into DNA, thereby interfering with the function of DNA. The blood concentration of FTD is maintained via TPI, which is an inhibitor of the FTD-degrading enzyme, thymidine phosphorylase.

Colorectal cancer (CRC) is the fourth most common cancer in the UK, with 41,100 new cases diagnosed in 2013. Approximately 25% of patients with CRC present with metastases at initial diagnosis and almost 50% will develop metastases; this contributes to the high mortality rates reported for the disease. The five-year survival rate of patients diagnosed with stage IV mCRC is about 11%.