Tanios Bekaii-Saab, MD
For a long time, patients with metastatic colorectal cancer (mCRC) had poor outcomes and very limited treatment options, said Tanios Bekaii-Saab, MD.
, he compared the mechanisms of action and toxicities of both therapies, and shared his views on the optimal sequencing of the 2 agents.
OncLive: How do regorafenib and TAS-102 compare?
: These are very different agents. Regorafenib is an agent that is essentially more of a biological multitargeted tyrosine kinase inhibitor. It hits multiple targets; it's what we call a “dirty drug.” It has too many targets.
TAS-102 is more of a traditional chemotherapy agent. It is oral—as regorafenib is—but it is a cytotoxic agent. It has some properties that allow it to work even when patients are exposed to 5-FU (5-fluorouracil) and fail.
Is there an understanding of the optimal sequencing for the 2 agents?
These agents were tested in very similar settings, but they have never been compared head to head.
Regorafenib was compared with placebo in a large study and it showed superiority to placebo in all parameters. TAS-102 was also compared with placebo and also showed an improvement in all efficacy parameters.
We don't have any guidance. The little bit that we do have comes from the RECOURSE study, which is TAS-102 versus placebo, and about 20% of the patients were already exposed to regorafenib. Those patients seemed to do as well those who were not previously exposed to regorafenib. We know that—if you give regorafenib first—TAS-102 preserves its activity. Unfortunately, we don't have that data with regorafenib.
We also have some hints about where regorafenib work best. There is the CONCUR study—which is an Asian study—looked at patients in which, of about 40% to 50% of them, did not have exposure to anti-VEGF or anti-EGFR therapies. What this study historically suggests compared with CORRECT—which was the initial regorafenib study—is that the deltas between regorafenib and placebo are bigger. This means that regorafenib seems to confirm a further benefit if moved up the line. The later we wait to introduce it, the less likely we are going to get the benefit.
With TAS-102, we have 2 hints. One comes from the RECOURSE study, which suggests that the patients who had less than 2 prior therapies didn't do as well as those who are more heavily treated. The TARA study, which is very similar to CONCUR and was done in an all-Asian population, showed very similar to what we saw in RECOURSE. This means that moving TAS-102 up the line didn't necessarily show a further benefit.
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