The European Commission (EC) has granted marketing authorization for combined trifluridine/tipiracil , formerly known as TAS-102, in the European Union (EU) for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents.

“Data from the pivotal RECOURSE study provides evidence that combination trifluridine/tipiracil may offer patients with refractory metastatic colorectal cancer extended survival as well as a reduction in risk of death compared to placebo,” said Professor Eric Van Cutsem, MD, PhD, Digestive Oncology, University Hospitals Leuven in Belgium. “The combination of trifluridine and tipiracil works by directly attacking the DNA of the tumour cells which reduces the growth of cancer cells. This approach fights the cancer differently to other previously given treatments, allowing us to delay cancer progression rather than cycling back through therapies that have already been used.”

“With this approval, we are delivering on a promise to bring a new treatment to patients with advanced metastatic colorectal cancer across Europe,” said Dr. U. Marion Schrenk, Head of Global Medical Strategy, Oncology at Servier, which markets trifluridine/tipiracil as Lonsurf. “[It] has also been shown to prolong progression-free survival and preserve performance status, allowing patients to make time for more moments that matter.”

There remains a high unmet need in the treatment of colorectal cancer (CRC), which was the second leading cause of cancer-related deaths in Europe in 2012, responsible for 215,000 deaths.

Approximately 25% of patients with CRC present with metastases at initial diagnosis and almost 50% of patients with CRC will develop metastases.

This contributes to the high mortality rates reported for CRC; the 5-year survival rate of patients diagnosed with stage IV mCRC is about 11%.

The decision from the EC follows the positive opinion issued by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommending the approval of the combination in February 2016.

Both the CHMP opinion and the EC decisions were based on data from the international, double-blind, placebo-controlled Phase III RECOURSE study, which investigated the efficacy and safety of combination therapy with best supportive care (BSC) compared to placebo with BSC in 800 patients with previously treated mCRC.

The study met the primary endpoint of statistically significant improvement in overall survival (OS).

RECOURSE is an international, double-blind, placebo-controlled Phase III study, which investigated the efficacy and safety of combined trifluridine/tipiracil with BSC compared to placebo with BSC in 800 patients with previously treated mCRC, among which 403 were treated in Europe.

The study met the primary endpoint of statistically significant improvement in OS.

Results demonstrated a 32% reduction in risk of death compared to BSC (HR=0.68; 95% CI: 0.58 to 0.81 p<0.001).

An updated OS analysis in 89% of events, presented at ASCO GI 2016, confirmed the clinically meaningful and statistically significant survival benefit compared to placebo with BSC.

This translates into a 31% relative reduction in the risk of death (HR=0.69; 95% CI: 0.59 to 0.81; p<0.0001) and an improvement of 2 months in the median OS.

The median OS for patients receiving the treatment was 7.2 months vs 5.2 months for placebo with BSC, this translated into 1-year survival rates of 27.1% and 16.6%, respectively.

The most frequently observed side effects (≥ 30%) were neutropenia, nausea, decreased appetite, diarrhoea, fatigue, anaemia, thrombocytopenia, increase in total bilirubin, alkaline phosphatase and ASAT levels, and leucopenia.

Source: Committee for Medicinal Products for Human Use