TRK Inhibitors for Advanced Solid Tumors


David S. Hong, MD, of The University of Texas MD Anderson Cancer Center, discusses the availability of TRK inhibitors to treat advanced TRK fusion-positive solid tumors, highlighting their safety and efficacy.

David S. Hong, MD: The standard approved indication for NTRK fusion is broad in the sense that patients with advanced cancers with NTRK fusions, identified by usually a CLIA [Clinical Laboratory Improvement Amendments]–certified test in the United States, can receive larotrectinib or entrectinib. Both drugs can target NTRK fusion and have shown significant efficacy in patients with NTRK fusion. Most of these patients will probably also have standard of care, and the thought is that they should probably undergo standard-of-care options before you try to give to patients with NTRK fusion. In rare settings, such as patients who don’t have standard of care, it is warranted that you can prescribe either drug. Overall, my experience is that these drugs are incredibly efficacious in patients who have NTRK fusion. In my experiences, these patients, regardless of the number of prior lines of therapy, will have an incredible benefit from either larotrectinib or entrectinib. There appears to be some differences between larotrectinib and entrectinib. Larotrectinib overall has a data set that is much more mature, and a higher number of patients seem to have been enrolled in the larotrectinib data set. The overall response rate appears to be higher, at least preliminarily with larotrectinib.

The adverse-effect profile is also very similar with these 2 drugs. Both of them have the vast majority of these patients having grade 1 and 2 toxicities, and both exhibit elevation in liver function tests. The vast majority of these patients will have mostly fatigue, which was the most common adverse effect associated with larotrectinib, and dysgeusia or changes in taste, which was also associated with entrectinib. Interestingly, both of them also will have specific adverse effects that are unique to the NTRK story in the sense that they will target the NTRK pathway. Both drugs exhibit dizziness or some level of ataxia. This dizziness and ataxia tends to be self-limiting over time; patients do tend to get better. Another common adverse effect with these drugs is that patients do gain weight, and that can be related to NTRK2 or NTRKB, which can modulate appetite and can increase appetite and weight gain. Otherwise, the overall drug adverse-effect profile of these oral drugs is incredibly well tolerated. Lastly, some of these patients will develop a pain syndrome that can be associated primarily with being off the drugs for a short period of time. This pain syndrome can be either relieved by standard opioid medications or actually redosing these patients back on the drugs.

Transcript edited for clarity.

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