NTRK: Front-Line and Second-Line Treatment Options for Patients With NSCLC

Rajwanth Veluswamy, MD, Icahn School of Medicine, New York, reviews his presentation at Great Debates and Updates in Lung Cancer covering front-line and second-line treatment options for patients with non-small cell lung cancer and NTRK fusions. 

Transcript:

Hi, my name is Rajwanth Veluswamy. I'm a thoracic medical oncologist at the Icahn School of Medicine at Mount Sinai in New York City. I'm here at the Great Debates & Updates in Lung Cancer, and today I spoke about [neurotrophic tyrosine receptor kinase] NTRK fusions. This is a very exciting field in lung cancer, mainly due to the pretty amazing responses we're seeing with TRK inhibitors. NTRK fusions are relatively rare fusions across cancers and especially in lung cancer, where it makes up probably around 0.5% to 1% of the mutations causing lung cancers. It's very important to test for these mutations, along with all the other actionable mutations in lung cancer, because the treatments can really impact the course for patients, as far as how efficacious these drugs are, and the tolerability of these drugs. And so it can really make a difference in your patient's lives.

It's very important to do comprehensive genomic testing, keeping in mind NTRK fusions. There are a couple of FDA-approved drugs that target NTRK, namely, larotrectinib and entrectinib, and these are approved in a tumor-agnostic indication. It doesn't matter what tumor it is, as long as it has that NTRK fusion. That's really quite landmark, and it speaks volumes to how effective these treatments are.

The response rates are well over 60%, 70%, and the durability, patients do very well on these drugs for quite an extended period. We're talking years. There's a specific side effect profile that we all need to get familiar with, with these drugs, and it's based on the mechanism of action. But with effective mitigation strategies, patients can do really well and tolerate these drugs. You can always turn to package inserts, and some of the available data where there's guidelines to follow about these side effects.

Ultimately, even as good as these first-generation TRK inhibitors are, resistance tends to develop, and we are learning more and more about the resistance mechanisms. The on-target resistance mechanisms have led the way to next-generation NTRK inhibitors that are in various stages of clinical development. in clinical trials right now, and they're really showing very early signs of good efficacy and tolerability. For a relatively rare tumor, we have several options, and they're all very, very good options. There's a lot to be excited about in this space.

Source:

Veluswamy, R. NTRK: Front-line and second-line options. Presented at: Great Debates & Updates in Lung Cancer; October 14-15, 2022; Brooklyn, New York.