Updates on Upfront Treatment of Metastatic Colorectal Cancer - Episode 5

Future Research and the Clinical Management of mCRC


Zev A. Wainberg, MD: In 2018, colon cancer treatment for metastatic disease hasn’t changed that much. There are certain improvements that we’re making. Certainly, supportive care has gotten better and our ability to handle patient toxicity has improved. To some extent, I think we are at a bit of a standstill with respect to treatment options. We have exhausted, for the most part, the group of patients who may benefit from immunotherapy, which includes the MSI [microsatellite instability] group. That is a very, very exciting piece of data. We’re seeing exciting prolonged responses and clinical benefits.

Second to that, I hope that we’ll go back and refine some of the molecular targets and spend the next few years focusing on those—including HER2, BRAF, and others—to develop treatment options for patients with these small subsets. The Holy Grail, which still exists, is to try to find a drug that helps KRAS-mutant patients. There is a whole surge of investigations looking into that, but they are probably not coming for another few years. We are looking forward to those when they become available.

The next few years are going to be important in working to tease out, in particular, whether there are any additional immunotherapy combinations that might work in this disease. We already know that the only real role for checkpoint inhibitors in colon cancer is in MSI disease. Now there’s a huge wave of second-generation checkpoint inhibitor studies in colon cancer, in which they’re being manipulated with either chemotherapy or other checkpoint inhibitors in an effort to turn some of these cold tumors hot. So that’s really the emphasis over these next few years—whether we can find a suitable partner, or another area, to go after.

Overall, my sense is that the next few years are going to be a bit disappointing in that regard. It’s not as simple as it appears to be. We’re hopefully going to go back to targeted therapies to start identifying new targets that may be amenable to certain drugs. There are big studies looking at BRAF inhibitors now. There are also big studies looking at HER2 inhibitors, and TRK, and all of these small subsets, which, admittedly, are very small. These are probably going to get teased out more in the next year or 2.

Transcript Edited for Clarity