Overview of Toxicity Associated With TKIs in Solid Tumors

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EP: 1.Overview of Toxicity Associated With TKIs in Solid Tumors

EP: 2.Understanding and Detecting TKI-Specific Hepatotoxicity

EP: 3.Vigilance Is Key in Mitigating TKI-Associated Hepatotoxicity

EP: 4.Reducing Adverse Events Through Dose Optimization

EP: 5.Novel Investigational Combination Strategies

EP: 6.Future Directions: Optimizing Care Through Combinations

Transcript:

Tanios S. Bekaii-Saab, MD: In our world, we’re moving more toward these oral medications, these tyrosine kinase inhibitors, which have multiple targets. These targets can be different among the different agents. When we look at the agents available to us in solid tumors overall, not just in GI [gastrointestinal] cancers, you have multiple classes of agents; many share targets. Others are more specific to a target, although it can hit other targets as well. For example, oral EGFR inhibitors are more commonly used in lung cancer, but for a little while, we used erlotinib as 1 agent in pancreatic cancer. I can see significant rash, diarrhea, mucositis, and occasionally even pneumonitis. The most common agents we use in GI malignancies are those that target VEGF and those with a point of entry for HER2 [human epidermal growth factor receptor 2] tyrosine kinase inhibitors.

Across the board, when you look at all the tyrosine kinase inhibitors, they’ve all induced some level of fatigue. For example, those that hit VEGF have wound-healing complications but also hand-foot syndrome reactions. It’s interesting to see varying degrees of that. For example, let’s take HCC [hepatocellular carcinoma], where we use lenvatinib, sorafenib, regorafenib, and cabozantinib. You can see that regorafenib would have the highest risk of hand-foot syndrome reaction. Lenvatinib has a lower risk, but you see a higher risk of hypertension because the VEGF is targeted at a higher level. For HER2 disease, we just presented data with tucatinib, a HER2-specific tyrosine kinase inhibitor.

This is an interesting agent compared with a lot of the others like lapatinib, lorlatinib, and others. This 1 is very specific to HER2. There’s very little targeting of EGFR, so you don’t have the rash. Or if you have it, it’s very faint and not as problematic. You have less diarrhea. These agents, although they can share similar pathways, some of them are more dominant on 1 target than others. That can also affect the levels of toxicities with tucatinib. You can see some left ventricular dysfunction in very rare cases, although I can most see the transient drops in ejection fraction that normalize. Across the board, we see some level of hepatotoxicity across all these tyrosine kinase inhibitors.

Transcript edited for clarity.