Precision Medicine: Key Updates for Treatment of NSCLC - Episode 15

NTRK Fusions in Non–Small Cell Lung Cancer

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Benjamin Levy, MD: I just want to briefly finish with 1 of the rarer genotypes among cancer: NTRK fusions. I’ll briefly review the data with both larotrectinib and entrectinib. The larotrectinib data were the poster child for a basket trial. They were taking patients irrespective of tumor type or histology, and if they had an NTRK fusion, they were all treated with larotrectinib. There were more than 17 different tumors treated. Incredibly, the age range of this trial was 4 months to 73 years. The large majority—more than half—were treated with either 2 or 3 lines of therapy prior to the drug being delivered. Not unlike the other targeted therapies we’re talking about, the response rates were anywhere from 70% to 80%. It is probably underrepresented in the lung cancer space. There were 3 or 4 young patients with other types of tumor sarcomas that were thought to be advanced stage, in whom they were able to give this drug, shrink it down, and do limb-sparing surgery for cure. This is an incredible advance. The responses were durable. There are some adverse effects with this drug, but it tends to be really well-tolerated overall. You do see some weight gain and hyperphagia that can be seen as part of the NTRK physiology, but overall it is a reasonably well-tolerated drug.

The second drug, entrectinib, published in The Lancet Oncology. There were roughly 50 patients with more than 12 tumor types in the study. It was another basket trial with response rates of 50% to 60%. We’ve already talked about some of the entrectinib adverse effects. I will be transparent, and say that I have not yet found an NTRK fusion, and I have not used these drugs yet. I’m still looking. I’ll turn it over. Becca, have you seen NTRK fusions? Have you used either of these drugs?

Rebecca Heist, MD: There have been 1 or 2 at my institution. I have not treated these patients. They’re exceedingly rare in lung cancer.

Benjamin Levy, MD: Yes. Josh?

Joshua Bauml, MD: What’s frustrating is that I actually treat salivary gland tumors as well. You would expect that I would have seen a patient with NTRK fusion, but I have not. I keep looking. I keep looking.

Lyudmila Bazhenova, MD: We have the most experience. I never found a lung cancer patient with NTRK fusion. I’m still looking, but since I have an NTRK-MET trial open at my site, I’ve seen gastrointestinal NTRK fusion. I’ve seen a wonderful response in an anaplastic thyroid cancer patient with NTRK fusion, where the drug clearly prolonged the patient’s life because he had a very bulky disease in the neck with respiratory symptoms. My experience with entrectinib is exactly as published. There is some perioral numbness when they start. An interesting bit of information about those drugs is, when you stop the drug for toxicity or whatever, a patient can have hyperalgia. They have a pain syndrome, and they get scared. Just be aware, if you hold the drug for any reason, and explain to your patient that they might have an exacerbation of pain that is not cancer related. Then, once you put them back on the drug, the pain goes away.

Benjamin Levy, MD: Those are all good points. Thank you, Lyuda, for your perspective on NTRK.

Transcript Edited for Clarity