Evolving Strategies for Advanced Colon and Rectal Cancers - Episode 10

Treatment Recommendations for Relapsed/Refractory mCRC


John L. Marshall, MD: Let’s move on to the refractory setting. Immune therapy has its place, but most of our patients won’t be candidates because we have relatively new agents, oral therapies in the refractory setting. Maybe talk a little bit about how you decide, when you’re seeing your patients, which medicines to use when and some of that data.

Christopher Lieu, MD: In the third-line and beyond settings, there really isn’t a right or wrong answer here. We have 2 relatively new FDA approvals for both regorafenib and TAS-102. As Tony had mentioned, we don’t like to do any cross-trial comparisons, but when you look at overall survival benefit, they seem similar between both trials. And these are both FDA approved options. And so, when you look at the patients that are treated with FOLFOX [folinic acid/fluorouracil/oxaliplatin].

And then FOLFIRI [folinic acid/fluorouracil/irinotecan hydrochloride] with or without an EGFR inhibitor, depending on sidedness, depending on RAS status, there’s no biomarker to really direct your care. So you do have the option to use either drug. Tony is going to talk a little bit about the dosing of regorafenib, which I think is a key aspect here of how to get our patients up to a therapeutic dose and keep them there in a way that doesn’t really truly affect their quality of life in a very adverse way.

But here, in this situation, you should have free reign to use either TAS-102 or regorafenib. The toxicity profile is something that we really discuss with our patients, in regard to what it is that they want to try next. Because in the absence of a clinical trial they’re likely to see both agents, as long as their performance status [PS] is preserved. And so in patients that have had massive cytopenias over the course of chemotherapy, TAS-102 may not be the right agent for them. For patients that have had really bad difficulty with some of the targeted agents that we use, then maybe regorafenib in that setting may not be right.

John L. Marshall, MD: Like fatigue and skin rash, and things like that.

Christopher Lieu, MD: Correct. But really, this is a decision between the provider and the patient because these are 2 very different drugs.

Howard S. Hochster, MD, FACP: Do you have any biases, depending on the patient’s general performance status and symptoms, on how you use the drugs? I mean besides presenting them as equal, you don’t have any particular practice?

Christopher Lieu, MD: My major concern if a patient has a really poor performance status is that they may be more susceptible to the fatigue and mucositis. So in that situation, you may be more likely to use TAS-102 compared with regorafenib.

John L. Marshall, MD: But these drugs don’t really work in the falling performance status, so they’ve got to be pretty good PS to start with. I think one of our areas of emphasis is using it before they start to fall.

Howard S. Hochster, MD, FACP: Right.

Transcript Edited for Clarity