Personalized Approaches to Treatment of Metastatic Colorectal Cancer - Episode 18

Novel Combinations Being Investigated for mCRC Treatment

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Current trials exploring novel combinations that show potential in making microsatellite stable tumors hot and amenable to response to immunotherapy in metastatic colon cancer.

Tanios S. Bekaii-Saab, MD: All of this excitement about immune therapy led us down the path to the question of, can we take microsatellite-stable tumors and make them hot, make them merely inflamed? Cathy, what do we know about the data? We've seen some data from Japan, initially, that looked intriguing with regorafenib and nivolumab, although it looked more interesting in gastric than in colorectal. There were some interesting responses in colorectal, and we've seen lenva [lenvatinib], pembro [pembrolizumab]. We're seeing the use of others that are looking interesting in a couple of patients but mostly not so. What do we know so far? Is there a path forward for MSS [microsatellite stable] and IO [immunotherapy]?

Cathy Eng, MD, FACP, FASCO: That's what we all hope for. I'm going to highlight the fact that you brought up regorafenib, Phase 1 of gastric and colorectal carcinoma, which was promising. It showed a response rate greater than 30% in colorectal cancer patients. But then Richard Kim at Moffitt Cancer Center presented his data on 25 or so patients and, unfortunately, could not duplicate those results. That was very disappointing. Other people have reported some of their own case series. There is data that is pending for the Phase 2 trial that was supposed to be completed, which was cut short. I don't have that formaldata. We see this intriguing Phase 1 data, then you take it to Phase 2, and it's hard to duplicate.

There are lots of other combinations that are being looked at. There was also the nivo [nivolumab]/ipi [ipilimumab] with eGFR [estimated glomerular filtration rate] therapy. That's another concept that's on the table. There are other intriguing but once again intriguing small studies. Whether or not we can make that have a significant benefit in our standard patient population is unknown at this time.

There's data I do want to highlight from the BRAF-mutated patient population associated with CMS1 [consensus molecular] subtype, suggesting that there is benefit for IR [infrared] therapy. That's why I incorporate it. Van Morris, who's my colleague and who I mentored when I was at MD Anderson, has a trial specifically for BRAF-mutated patients. We do want to highlight the fact that there may be some benefit in some selected patient populations. I’ve never had a CMV [cytomegalovirus] of 190, ever.

Tanios S. Bekaii-Saab, MD: That was a very interesting case. We think there's a path forward but in select patients. Maybe the way we've done it previously is just pouring all these MSS's in 1 basket was not the right way to do it. Moving forward, selecting better those patients who fit into these different baskets.

Transcript Edited for Clarity