Post-Conference Perspectives: Sequencing in the Current mCRC Paradigm - Episode 4

Later-Line Treatment for mCRC: Regorafenib or TAS-102?


Howard S. Hochster, MD, FACP: For patients who have received all the standard drugs—this could be third line or it could be fourth line, depending on how you use your anti-EGF antibodies—today we’re looking at a couple of drugs that are approved in that setting. One is regorafenib and the other is TAS-102.

So these are pretty different drugs with pretty different toxicity profiles. The regorafenib is a multikinase tyrosine kinase inhibitor, so it has a lot of the TKI type toxicities of hand-foot syndrome, rash, and fatigue. I think it’s a difficult drug to give to colon cancer patients if they’re already beginning to have systemic symptoms and they aren’t too robust. I think for the more robust patients, it’s probably worthwhile giving them a try of this drug. There is certainly a tail on the benefit curve such that some people really can stay on it for 6 to 12 months and really benefit from it. That would be maybe up to 20% of patients.…Particularly with some of the new dosing information from the ACCRU trial, I think that it’s probably easier to give the drug starting at 50% dose and then escalating, so I’ve been doing that a little bit more.

The TAS-102 is antimetabolite. That’s a little different than 5-fluorouracil [5-FU] but certainly seems to be beneficial in patients who have gotten a lot of 5-FU previously. And I think there are a lot of opportunities to combine that drug with irinotecan or with oxaliplatin. We’re presenting a poster, here at the GI [Gastrointestinal Cancers Symposium] ASCO [American Society of Oncology] meeting, with my colleagues from Yale of a study that we did with TAS-OX, TAS-102 with oxaliplatin. That’s tolerated pretty well. I think there are more opportunities to eventually move TAS-102 into earlier-line therapies.

Transcript Edited for Clarity