New Biological Insights and Recent Therapeutic Advances in the Management of Lung Cancer: A Clinical Investigator Think Tank
A patient whose tumor was ALK wild type by FISH testing but subsequently identified by NGS as ALK rearranged
1:40 minutes.
TRANSCRIPTION:
DR CARBONE: I had a patient who I tested for ALK and EGFR and was negative for both. Treated him for a long time. I gave him carbo/pem. He did really well. Then started to progress, and I sent a Foundation Medicine panel on him. It came back ALK-positive. DR LOVE: He responded to ALK treatment? DR CARBONE: And then I gave him crizotinib and he responded beautifully. DR LOVE: Scary. DR SPIGEL: Yes, I mean, but what you don’t know is whether that evolved or whether that was always there. DR CARBONE: So it turns out that there are now data that about 25% of next-gen-positive ALK is FISH-negative and that these people respond to ALK-targeted therapies. So I think we’re still learning about the best — DR LOVE: Has that been presented and published? DR CARBONE: Yes. It was presented as a poster last year. Foundation had about 15 cases of this. And they showed clear PET scan responses in these FISH-negative, sequence-positive ALK cases. DR SPIGEL: Though there are other cases that are FISH- or IHC-positive and missed on next-gen sequencing, because rearrangements are so hard to find on next-gen sequencing. DR CARBONE: Right. DR SPIGEL: It’s hard to know what assay is going to trump this. And they’re going to have to piece them together. DR CARBONE: So we think genetic analysis is absolute, it’s black and white, but it turns out that it’s not so easy. DR OXNARD: And one of the major risks of these assays is the false discoveries. Right? DR CARBONE: Mm-hmm. DR OXNARD: You find some rare ALK mutation that means nothing, and you’re giving your patient crizotinib, but it has no biological meaning. And you get a lot of information from these tests — DR CARBONE: Right. DR OXNARD: — which might lead you down the wrong path, not the right path. |