Advanced CRC: Pushing the Treatment Paradigm Forward

Transcript:

Wells A. Messersmith, MD, FACP: The evidence in metastatic colorectal cancer continues to come from large clinical trials. I would say the most striking example in the last few years has been the 80405 trial, which is a large study that looked at what the best first-line biologic to use is and taught us that right-sided versus left-sided tumors should be treated differently from each other. That has been practice changing. It changed the guidelines and has been an important addition to our knowledge in terms of what the best therapy to use is.

I’ll tell you, the second most important thing has been immunotherapy and the lesson that microsatellite-high patients benefit from immunotherapy. More recent data show that combination immunotherapy is especially effective in this patient population. Combining CTLA4 plus PD-1 inhibitors seems to be effective. There are ongoing trials looking at PD-1 or PD-L1 inhibitors in the adjuvant setting and in the first-line setting, because those are approved for second-line therapy and above, and so we’ll see how those trials pan out.

For ASCO 2018, I would say the bottom line is that there have been multiple incremental benefits looking at a few different themes. One theme is biomarkers, and we continue to have additional subsets of colorectal cancer just as with other diseases. We knew about BRAF, and we’ve known about NRAS and KRAS. We’re starting to learn now about HER2, and we’re starting to get more information about MSI-high patients. I think as time goes on, we’ll see more and more of these biomarkers. Of course, an emerging question is, can we just use circulating tumor DNA, or do we really need to biopsy patients again and again to figure out what’s going on in their body? A second theme is immunotherapy and whether combination immunotherapy will be useful for these patients. Another theme is sequencing of therapy. In other words, does starting with drug A and going to drug B or using B then A make a difference? What’s the best maintenance approach? These are the kinds of questions that have been addressed in ASCO 2018.

Transcript Edited for Clarity