Third-Line Regorafenib and TAS-102 in mCRC

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A number of treatment options are available for patients with metastatic colorectal cancer (mCRC) who have progressed on two prior lines of therapy, such as bevacizumab, EGFR antibody therapy for RAS wild-type patients, 5-FU, oxaliplatin, and irinotecan. In the third-line setting, regorafenib is beginning to gain recognition, says John Marshall, MD. However, understanding how to use this multikinase inhibitor is important when treating patients.

In September 2012, the FDA approved regorafenib as a treatment for patients with mCRC following prior therapy. This decision was based on findings from a 760-patient phase III study (Study 14387) that demonstrated a statistically significant prolongation in overall survival (OS) with regorafenib compared with placebo. The median OS with regorafenib was 6.4 versus 5.0 months with placebo (HR = 0.77; P = .0102). The median progression-free survival (PFS) was 2.0 versus 1.7 months for regorafenib and placebo, respectively.

When administering regorafenib, it is important to monitor for early side effects during the first few weeks of therapy, as this is when adverse events appear to be the worst. According to Axel Grothey, MD, an ongoing study is looking at reducing the 160-mg starting dose to evaluate whether that makes toxicities more manageable. This is a drug for patients with good performance status, Grothey emphasizes. Also, preemptive management of skin toxicities is important.

The oral fluoropyrimidine TAS-102 (tipiracil hydrochloride) is another promising third-line agent on the horizon, says Dan Haller, MD. In the phase III RECOURSE study, the median OS was 7.1 months with TAS-102 compared with 5.3 months with placebo (HR = 0.68; P <.001). The PFS with TAS-102 was 2.0 versus 1.7 months with placebo (HR = 0.48; P <.001).

Based on these findings, the FDA accepted a new drug application for TAS-102 in February 2015. The agency is scheduled to make a final approval decision on the chemotherapy by December 19, 2015. Assuming that TAS-102 receives FDA approval, Haller sees it as a good first choice in the third-line setting.

TAS-102 seems to have less toxicity compared with regorafenib, Haller notes. While there is a higher incidence of myelosuppression with TAS-102 than with regorafenib, there is no hand-foot syndrome. Compliance with the dosing schedule is another important detail to monitor with TAS-102, notes Herbert Hurwitz, MD.

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