Future Perspectives on HER2+ Metastatic Colorectal Cancer

Transcript:

Tanios S. Bekaii-Saab, MD: I think we pretty much have seen how all these targeted strategies are emerging in colorectal cancer. A big focus of course on HER2-amplified tumors. The biggest excitement is, as with all biologics, once we start seeing this biologic activity for certain agents present in more refractory setting, we always think about the saying that [if] you hit biology early, you’re going to do essentially the best. We hope by bringing all these agents to early lines of therapy that the significant benefits we’ve already seen in later lines are going to translate into bigger benefits when we hit this in the early lines. We’ve seen that with several agents. We’re hoping to see that with HER2-amplified tumors through the MOUNTAINEER-03 study [NCT05253651], which is essentially randomizing patients to FOLFOX [folinic acid, fluorouracil, and oxaliplatin] plus tucatinib [with] trastuzumab vs FOLFOX [regimen] plus standard of care. So that’s one element.

Understanding a little bit more how to best sequence patients with HER2-amplified tumors. Understanding a little bit more about the toxicities and how to manage the toxicities of the various agents. A lot of it is already common knowledge. A lot of it is not. As we start using more and more of these agents in clinic, this becomes a learning curve. Then a number of other targeted strategies from targeting KRAS to targeting BRAF V600E and others are also moving into the first line. Although we’re still covering about 20% of patients with colon cancer with targets, the other 80% remain in need of finding a target that’s relevant, at least that we can target directly. There is an emergence of G12D [mutation] inhibitors that are making it into the clinic, which is the most common KRAS mutation. It’s a long way to go, but it’s making its way.

The other one is microsatellite stable tumors and the use of IO [immuno-oncology]. At this point of time, it doesn’t appear to be beneficial to use immunotherapies in patients with microsatellite stable, even when adding them to tyrosine kinase inhibitors or VEGF inhibitors or chemotherapy. We do have studies that show that there may be some benefit for some of these patients, a small subgroup of patients with later separation of the curves on studies that have been presented or published. What we’ve seen from a study called AtezoTRIBE [NCT03721653] is that the utilization of immune cell score, so spatial representation of relevant biomarkers and cells, can actually predict for who may benefit from the addition of IO to first-line chemotherapy plus bevacizumab [Avastin]—that’s about 15% of the patients. We continue to add more and more options to our patients. I think the future looks so much brighter for our patients and we’re getting closer and closer to closing the gap to these other 80% of patients.

Transcript edited for clarity.