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Goals of Therapy in Refractory Colorectal Cancer

Panelists:John L. Marshall, MD, Georgetown University Hospital;Tanios Bekaii-Saab, MD, Mayo Clinic;Cathy Eng, MD, FACP, MD Anderson Cancer Center;Daniel G. Haller, MD,FACP,FRCP, University of Pennsylvania;Tara E. Seery, MD, UC Irvine
Published Online: Tuesday, Aug 30, 2016



Transcript:

John L. Marshall, MD:
Dan, it’s now 2 years after our first-line story. The patient has a favorite parking space in the parking lot, they know the front desk people, they know the people in radiology, and they come in and they now have progression of disease on first- and second-line. What is our goal of therapy now in this PS (performance status) 1.75 patient that’s coming in? Mediport is in place, they have a little neuropathy, their skin’s a little dry, and maybe their hair looks like mine. What’s our goal of therapy right now?

Daniel G. Haller, MD: I think the RAS story drives that, as well as what they got before. If you have a RAS-mutated patient who got FOLFOX/bevacizumab or FOLFIRI/bevacizumab, and they’re not getting an EGFR agent, they’re now in line for TAS-102 or regorafenib. The drugs were developed in exactly the same schema with exactly the same number of patients. It was virtually the same benefit, just different toxicities.

John L. Marshall, MD: Is our goal different than it was in the beginning?

Daniel G. Haller, MD: It’s prolonging that 1.75 PS. It’s not shrinking tumors. It’s prolonging survival, slowing the decline. And that’s what was shown in the TAS-102 study. Dropping from 0 to 1 to 2 was longer in the group that got treated than those with a placebo. For people who got sequential FOLFIRI/bevacizumab, then FOLFOX/bevacizumab, and then an EGFR agent, they might be in fourth- or fifth-line therapy. I think in the CORRECT trial with regorafenib, the average was about 4 lines of therapy, right?

Cathy Eng, MD: Yes.

Daniel G. Haller, MD: So, that’s the group we’re treating. I think one of the issues, in looking at the benefits of these “last-line” drugs, is that some of them were third-line and some of them were sixth-line. It would be good to look at the variability of outcomes in those patients.

John L. Marshall, MD: Does that patient have a different goal? I always think of it as that patient in the frontline wants to be aggressive, that’s the language. Is the patient different now? They still want to be cured.

Cathy Eng, MD: I think the patient needs to be a little bit more realistic about what the goals are when we’re talking about third, fourth, or fifth lines of therapy. Once again, the quality of life is of utmost importance, but we’re really trying to help them prolong their survival. Honestly, if we can keep them on with good quality of life and with good outcomes, that’s the goal. We can potentially put them on a clinical trial down the road as well.

John L. Marshall, MD: We get a fairly high percentage, in our kind of center, of patients who make it to this line of therapy, too. But, we all have patients that don’t. They get to this point and either from a PS perspective or from their emotions, they don’t want to do it, right? So, there’s a fall-off, but I think almost everybody is getting first- and second-line.

Daniel G. Haller, MD: One thing that we did at JCO—and I was working on it—is we included the protocol in every large trial so that you could look and say, “Could my patient have entered this study?” When I talk about TAS-102 or regorafenib, I really try to get people to use that algorithm of how those patients got into the study. My feeling is that if you’re putting a patient who’s really got a performance status of 2, a low creatinine clearance, and bad experiences with other drugs, and you give them TAS-102, for example, they’re likely to have even less benefit and more toxicity. So, some patients should not be treated. I think with the newer drugs, you have to be a little bit more rigid about how you treat them.

Transcript Edited for Clarity

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Transcript:

John L. Marshall, MD:
Dan, it’s now 2 years after our first-line story. The patient has a favorite parking space in the parking lot, they know the front desk people, they know the people in radiology, and they come in and they now have progression of disease on first- and second-line. What is our goal of therapy now in this PS (performance status) 1.75 patient that’s coming in? Mediport is in place, they have a little neuropathy, their skin’s a little dry, and maybe their hair looks like mine. What’s our goal of therapy right now?

Daniel G. Haller, MD: I think the RAS story drives that, as well as what they got before. If you have a RAS-mutated patient who got FOLFOX/bevacizumab or FOLFIRI/bevacizumab, and they’re not getting an EGFR agent, they’re now in line for TAS-102 or regorafenib. The drugs were developed in exactly the same schema with exactly the same number of patients. It was virtually the same benefit, just different toxicities.

John L. Marshall, MD: Is our goal different than it was in the beginning?

Daniel G. Haller, MD: It’s prolonging that 1.75 PS. It’s not shrinking tumors. It’s prolonging survival, slowing the decline. And that’s what was shown in the TAS-102 study. Dropping from 0 to 1 to 2 was longer in the group that got treated than those with a placebo. For people who got sequential FOLFIRI/bevacizumab, then FOLFOX/bevacizumab, and then an EGFR agent, they might be in fourth- or fifth-line therapy. I think in the CORRECT trial with regorafenib, the average was about 4 lines of therapy, right?

Cathy Eng, MD: Yes.

Daniel G. Haller, MD: So, that’s the group we’re treating. I think one of the issues, in looking at the benefits of these “last-line” drugs, is that some of them were third-line and some of them were sixth-line. It would be good to look at the variability of outcomes in those patients.

John L. Marshall, MD: Does that patient have a different goal? I always think of it as that patient in the frontline wants to be aggressive, that’s the language. Is the patient different now? They still want to be cured.

Cathy Eng, MD: I think the patient needs to be a little bit more realistic about what the goals are when we’re talking about third, fourth, or fifth lines of therapy. Once again, the quality of life is of utmost importance, but we’re really trying to help them prolong their survival. Honestly, if we can keep them on with good quality of life and with good outcomes, that’s the goal. We can potentially put them on a clinical trial down the road as well.

John L. Marshall, MD: We get a fairly high percentage, in our kind of center, of patients who make it to this line of therapy, too. But, we all have patients that don’t. They get to this point and either from a PS perspective or from their emotions, they don’t want to do it, right? So, there’s a fall-off, but I think almost everybody is getting first- and second-line.

Daniel G. Haller, MD: One thing that we did at JCO—and I was working on it—is we included the protocol in every large trial so that you could look and say, “Could my patient have entered this study?” When I talk about TAS-102 or regorafenib, I really try to get people to use that algorithm of how those patients got into the study. My feeling is that if you’re putting a patient who’s really got a performance status of 2, a low creatinine clearance, and bad experiences with other drugs, and you give them TAS-102, for example, they’re likely to have even less benefit and more toxicity. So, some patients should not be treated. I think with the newer drugs, you have to be a little bit more rigid about how you treat them.

Transcript Edited for Clarity
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