TRK Inhibitors in Lung and GI Cancers - Episode 5

Approaching Genomic Testing for NTRK Fusions

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John L. Marshall, MD: Luis, Dr Raez, let me let you take the lead on this in terms of the mechanics of testing. We’ve all hinted at it—some do it internally, some are sending it out. Can you give us a sense of how one can get NTRK testing done?

Luis E. Raez, MD: We have several options, as somebody else mentioned. I think it was Jyoti. For example, we can do RT-PCR [reverse transcription polymerase chain reaction]. We can do RT-PCR to find the fusions. We can do FISH [fluorescence in situ hybridization] testing to find the fusions. We can do DNA sequencing, and lately we’re doing RNA sequencing. So now we have 4 options. How we deal with this, and what is the best approach? It actually depends. ESMO [European Society for Medical Oncology] has a recommendation published last year about this, but these are common sense.

For example, if this is a tumor that is very uncommon—lung cancer, colon cancer, breast cancer—they have a very low prevalence of NTRK fusions. The best thing we can do is to do the whole sequence, the whole DNA sequence. We also have discovered in the last 3 or 4 years doing that for NTRK that the DNA sequence may not be as complete or comprehensive as the transcriptome sequencing, the RNA sequencing.

That’s why we have platforms at our center that run both, the DNA sequencing and then the RNA sequencing, to touch any possibility or any fusion that has not been discovered. That’s for uncommon tumors. When you have 1 of these tumors that are very rich in NTRK, like mammalian—salivary cancer, secretory carcinoma of the saliva, secretory cancers of the breast, congenital lymphomas in kids or fibrosarcomas—you know that the prevalence of NTRK is very high, maybe 90%. So you can shoot straight, you can do RT-PCR, you can do FISH. For example, the salivary cancers are very high in NTRK3, so you can go straight and try to find that genetic aberration. That way maybe you don’t have to do a whole sequencing.

The last option we have—option No. 3, which not very common—we used to do before. We used to love FISH testing. Oncologists love FISH testing for breast cancer, but when we started to do lung cancer, we learned about that FISH is good for ALK. Then we discovered that maybe FISH is good for ROS. But it’s too cumbersome; there are too many FISH testings now. We have ALK, ROS, NTRK, and soon RET, so it doesn’t work.

That’s why the developing of immunohistochemistry is a very good option, because the problem is the amount of use of the tissue, that there is not enough tissue to look for other genetic aberrations. But some people have been successful publishing data; that antibody for NTRK can probably catch more than 90% of genetic aberrations. Maybe that’s an option for a center that doesn’t have the technology for RNA sequencing.

John L. Marshall, MD: Yeah, but what you just described is complicated. I can barely keep track of how to get FOLFOX [folinic acid, 5-flourouracil, oxaliplatin].

Transcript edited for clarity.