Oral Fluoropyrimidine TAS-102 in Refractory mCRC

For High-Definition, Click

The oral fluoropyrimidine TAS-102 represents a potential new treatment option for patients with refractory metastatic colorectal cancer (mCRC), explains Marwan Fakih, MD. The agent, which contains the thymidine analogue trifluorothymidine (TFT) and a thymidine phosphorylase inhibitor (TPI), received an FDA fast track designation in the refractory setting in October. Earlier this year, the FDA accepted a new drug application for the drug, placing a final approval decision for TAS-102 as December 19, 2015.

TAS-102 works differently than fluorouracil (5-FU) and should not be considered a "me-too" drug, remarks Fakih. TAS-102 works by intercalating into DNA, resulting in a malfunction of tumor cell proliferation. Based on preclinical data, cells that are resistant to 5-FU can be responsive to TAS-102.

A preceding phase II study randomized 72 patients with mCRC in a 2:1 ratio to TAS-102 or placebo after progression on or intolerance to systemic chemotherapy. In this analysis, TAS-102 significantly improved overall survival (OS) compared with placebo (median OS, 9.0 months vs 6.6 months) and significantly reduced the risk of death (HR = 0.56; P = .0011), leading to the initiation of the 800-patient phase III RECOURSE study.

In the RECOURSE, which was recently published in The New England Journal of Medicine, the median OS was 7.1 months with TAS-102 compared with 5.3 months with placebo (HR = 0.68; 95% CI, 0.58-0.81; P <.001). The median progression-free survival (PFS) with TAS-102 was 2.0 versus 1.7 months with placebo (HR = 0.48; 95% CI, 0.41-0.57; P <.001).

TAS-102 was not only statistically superior to placebo with an improvement in overall survival, but it was also well tolerated, Fakih adds. The main side effect was bone marrow suppression, which should be monitored in patients receiving the chemotherapy.

If approved, TAS-102 or regorafenib could be administered for a patient who has exhausted other systemic therapies. The choice of treatment could be based on side effect profiles, notes Fakih, in terms of avoiding either skin toxicity or myelosuppression. In addition, Fakih sees a potential for sequencing TAS-102 and regorafenib.