Adjusting the Lines of Therapy Indication in mCRC

Transcript: John L. Marshall, MD: I think about lines of therapy. I wish we could get away from that a little bit. And you’re saying that you’ll use a checkpoint in frontline, basically is ignoring the line of indication, right, the line of therapy indication.

Tanios S. Bekaii-Saab, MD: If I can get away with it.

John L. Marshall, MD: Right, and we can usually nowadays. But sometimes not. But I also think; so CAPE/BEV [capacitabine/bevacizumab] frontline. That’s an OK line of therapy, frontline. All the way to FOLFIRINOX [fluorouracil/irinotecan/oxaliplatin]/BEV or EGFR therapy. So if we fast forward to second line, when I think about the menu of medicines, I actually am increasingly including the oral therapies, REGO [regorafenib] and TAS-102, in earlier lines of therapy. The more I look at the data around that the drugs do not work in patients who are declining, and we never really catch people in that setting; so if I wait too long I’ve blown it. Whereas I think chemotherapy has a better shot at that, of pulling a patient out of a nosedive with a response. So I’ve kind of, in some ways in that asymptomatic lower tumor burden patient, thought about more use of the REGO and the TAS. And then the REVERCE trial, which kind of half way says that’s not crazy.

Tanios S. Bekaii-Saab, MD: And it makes sense.

John L. Marshall, MD: But we think of these drugs as salvage and I really think we need to let go of that term and just think of them as drugs that are active in colorectal cancer and play them when you want to play them. And we have the luxury of being only focused in a certain number of diseases, whereas a person out there who’s taking care of everything I’m sure will feel a lot less comfortable bringing some of those medicines forward. Do you think that is a trend that’s happening … you’ve done a lot of the work to drive some of that.

Tanios S. Bekaii-Saab, MD: I think, as you said, REVERCE definitely does tell us that regorafenib before cetuximab is an option that’s feasible, reasonable, does not adversely affect outcome. If anything, it shows an improvement in outcome. But that still has to get validated. So, yes, REVERCE is very intriguing.

When we look at the history of development of regorafenib, we look at a couple of studies. Specifically, CORRECT and CONCUR. And what CONCUR suggests in an Asian population that has seen less treatment, that the delta was much more interesting than the CORRECT.

John L. Marshall, MD: Yes, there’s less biologic too.

Tanios S. Bekaii-Saab, MD: Less biologics.

John L. Marshall, MD: So in some of those patients this was the first VEGF inhibitor, 1 of the many targets in REGO....

Tanios S. Bekaii-Saab, MD: Absolutely. On it’s own.

John L. Marshall, MD: I agree with you. I think it’s very profound data to say it’s a more active drug.

Tanios S. Bekaii-Saab, MD: Exactly. And I have a different view on TAS-102. I think TAS-102 is effective but it’s still a cytotoxic therapy, it’s a chemotherapy. It’s not a biologic modifier. And so in many ways I think TAS-102 maintains its activity across lines of therapy. The biologics seem to actually be more conducive to somebody, especially when given on their own, because that’s how we give REGO, if you move it earlier.

So I absolutely agree. We can’t let those patients; it was interesting in our REGO study, when we looked at patients who actually were able to get to 3, to the third cycle, they had an average survival of 1 year. Now these are patients that when we discuss them we talk about, well is it right to add 1 month of survival or 1-and-a-half months of survival? These are patients that if they do well, they do extremely well.

John L. Marshall, MD: Well, that’s where I’m going with this. So we’ve got small lung METS [metastases] and some small liver METS, and they’re progressing. CEA [carcinoembryonic antigen] is going up a little and 5 millimeters, everything’s changed a little bit.

Do I wholesale go to an irinotecan- or an oxaliplatin-based regimen versus now is a window to try something like this?

Transcript Edited for Clarity