Choosing Among Zongertinib, Sevabertinib, and T-DXd in HER2-Mutant NSCLC

Yasir Elamin, MD, an associate professor of thoracic medical oncology at The University of Texas MD Anderson Cancer Center, compares zongertinib, sevabertinib, and trastuzumab deruxtecan (T-DXd) for HER2-mutated lung cancer. With no head-to-head evidence establishing superior efficacy, Dr. Elamin emphasizes shared decision-making based largely on differences in safety profiles, including EGFR-related diarrhea and rash with sevabertinib, liver enzyme abnormalities with zongertinib, and the risk of interstitial lung disease with T-DXd.

Transcript:

Dr. Elamin: My name is Yasir Elamin. I’m an associate professor of thoracic medical oncology at MD Anderson Cancer Center in Houston, Texas.

Now that first-line sevabertinib data are available alongside zongertinib, what can we responsibly compare between the studies, and what conclusions should we avoid drawing?

Dr. Elamin: So I think all these three agents are great agents: sevabertinib, zongertinib, T-DXd. Of course there are differences in the mechanism of action. Zongertinib is an irreversible HER2 inhibitor that is HER2-mutant selective, while sevabertinib has activity across the EGFR family. And of course T-DXd is a HER2 ADC.

Again, they’re all great options, and I think what we need to be doing now that we have all these options available is to have shared decision-making with our patients. There is great deal of similarity in terms of their efficacy. So, I do not think that we have data to support which one is better in terms of efficacy. They have not been compared head-to-head.

However, there are clear differences in terms of their safety profile. For example, with sevabertinib, we do see more EGFR-related toxicity, such as diarrhea and skin rash and so on. While with zongertinib, we do see some liver enzymes derangement. Although this, these were at low rates or low levels.

With T-DXd, we do see some ILD, interstitial lung disease, which would be extremely important in the context of lung cancer. I think we are clearly making progress in treating HER2-mutated lung cancer. All these options are great. The differences are mainly in the safety profile.