Progression of Treatment in Colorectal Cancer - Episode 7
Wells Messersmith, MD:This case is just a classic colorectal cancer case that shows some of the good things that are going on and some of the challenges for the field. First of all, we have options. We have 13 different drugs, if you start to consider the immunotherapy drugs for MSI-high patients or deficient mismatch repair patients. So, we have a lot of different agents and a lot of different combinations, and if you think about 20 years ago, when patients lived 3 to 6 months with this disease, now patients are living more than 36 months if you’re left-sided, for instance, andRASwild-type. So, there’s a lot of reason to be somewhat comforted by the fact that we’ve quintupled survival from before all these agents were used.
On the other hand, this points to a lot of deficiencies in the field. So, first of all, which cytotoxic backbone should we use? We don’t have any predictive test for that. There are some arguments about ERCC1 and topoisomerase, etc, but none of those have really panned out in large trials. The choice of a cytotoxic backbone is still completely empirical, which is surprising in the 21st century.
Second, we don’t know what targeted therapy to use, especially forVEGFR, so when you use bevacizumab, ziv-aflibercept, ramucirumab, or even regorafenib to a pointalso it has antiangiogenesis properties—we really need biomarkers to predict who’s going to benefit from those. And we don’t have them. So, there are no tests you can send to ask, “Should I give this patient this expensive therapy? Granted, the side effects usually aren’t too bad, but should I be giving that?” It’s largely empirical.
And the third is that this patient was microsatellite stable, so they do not benefit, as far as we can tell so far. There are some trials going on, but they don’t benefit from immunotherapy, and that has been a very frustrating thing across the field. Why doesn’t colorectal cancer respond to immunotherapy the same way that other diseases do? We know that deficient mismatch repair and microsatellite-high patients, they benefit, but they’re only 4% to 10% depending on what you’re looking at. So, that has been a frustration as well. For over 90% of the patients, we don’t have effective immunotherapy, and so it has been a great deal of frustration in terms of moving the field forward.
On the good side, there are 13 drugs, some of them biomarker driven, quintupling of survival. On the bad side, there are still no good immunotherapy options for microsatellite-stable patients, no predictive tests for cytotoxic therapies, and no predictive tests for angiogenesis inhibitors. In this case, I think that wraps up many of those themes all in one.
Transcript edited for clarity.