Identifying Common Toxicities With Targeted Therapies in GI Malignancies

In an interview with CancerNetwork®, Rona Yaeger, MD, gastrointestinal medical oncologist and early drug development specialist at Memorial Sloan Kettering Cancer Center in New York, New York, spoke about common toxicities that might emerge with targeted therapies, including BRAF, KRAS, and EGFR inhibitors, when treating patients with gastrointestinal (GI) malignancies. The discussion was contextualized by a session she delivered titled “Targeting BRAF, KRAS, and HER2 in GI Tumors” at the 43rd Annual Chemotherapy Foundation Symposium in New York, New York.

Yaeger began by explaining that targeted therapies are mechanistically different from chemotherapy, with the former offering more specificity but unique toxicities. One common type, skin toxicity, requires proactive management, with Yaeger’s team working with dermatology to manage symptoms.

Additionally, she highlighted the approval of encorafenib (Braftovi), which has been shown to counteract acneiform rash events that emerge from treatment with cetuximab (Erbitux). Although these patients may not experience rash, dry skin may be common, with her team advising patients to moisturize and limit sun exposure. Yaeger concluded by highlighting diarrhea events that occur with these treatments, which can be proactively monitored for and treated with antidiarrheal agents.

Transcript:

Targeted therapies work differently from chemotherapy, and rather than hitting all the rapidly dividing cells, they are more specific and may have unique toxicities, and the toxicities vary across the targets for some treatments such as EGFR inhibitors or RAS inhibitors. Entering the clinic, skin toxicity is a key [adverse] effect, and we try to be proactive in managing that, both by giving preventive medications, such as using antibiotics, and involving dermatology when patients have toxicity.

With the BRAF [inhibitors]––with approval for encorafenib––generally, it does not cause the acneiform rash and it seems to oppose the effect of cetuximab. Patients getting encorafenib and cetuximab do not tend to have many rashes, but dry skin is common, and we tell patients to moisturize and be careful with sun [exposure]. Some of the targeted therapies can also cause diarrhea. That’s a common [adverse] effect, and again, it’s good to be proactive, make sure patients are aware, and we can give antidiarrheal agents.

Reference

Yaeger R. Targeting BRAF, KRAS, and HER2 in GI tumors. Presented at: 43rd Annual Chemotherapy Foundation Symposium; November 12-14, 2025; New York, NY.