Maurie Markman, MD: Again, this is a role for the pharmacists here. Again, this changes so fast, it’s hard to keep up with. Wendel Naumann, MD: In the recurrent setting based on the QUADRA data. Maurie Markman, MD: In the recurrent setting. Wendel Naumann, MD: Was it this week that we got an indication for HRD-positive patients? It’s not been decided yet, but certainly some of the data suggest potential relevance, so I think we all need to stay tuned. That may or may not continue in the frontline setting, so it may actually be, this type of testing may be required as per the FDA. PARPs have been approved broadly in the recurrent setting. Maurie Markman, MD: We’re going to talk a little bit about the recurrent setting later, but as of today, FDA approval does not require this testing. I guess these tests are how you sequence them, and how you pay for them is the other issue. But we don’t know of any data that suggest they don’t respond just as well as PARP inhibition. SOLO-1 included somatic mutations, but there were only a couple in the entire trial, so we don’t have high quality data on that. The germline is probably 10% to 15%, somatic is about half of that. Wendel Naumann, MD: In addition to somatic, right. Michael Birrer, MD, PhD: In addition to somatic. So they do need germline testing based on a high quality panel. You will miss some germline tumors if you rely on Foundation Medicine or Caris Life Sciences. I think it’s important to understand that you cannot always rely on the sequencing to look for germline tumors. It doesn’t really predict in recurrent disease, after exposure to PARP sensitivity. So if you’ve got a patient on a PARP inhibitor, they grow through the PARP inhibitor, they’re now resistant, the HRD assay is of no use because the scar remains. The final point I would make is because you’re looking at what’s called a genomic scar, the loss of heterozygosity, that’s permanent. So we’re going to be seeing physicians using these assays more and more. And I think the ESMO presentations really reinforced it. I don’t use them that much, but my colleagues do and they certainly correlate with an increased benefit from PARP inhibitors. The Myriad assay adds something called telomeric imbalance to it and also large-scale transitions, which are just other measures of damaged DNA.
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And the basis of that is that presumably if you have a tumor that has homologous recombination problems, you’re going to lose a lot of pieces of DNA.
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And they’re based upon looking for loss of heterozygosity within the tumor. But you should be aware that there are at least 2 HRD assays, 1 by Foundation Medicine, 1 by Myriad Genetics. I want to look for Fanconi genes and their mutations.
#Hrd test full#
Full disclosure, I’m still a sequencing kind of guy.
#Hrd test trial#
Michael Birrer, MD, PhD: This is an important topic, particularly after the ESMO clinical trial presentations. Mike, you want to talk about that a little bit? But then there’s this conversation about HRD and then HRD testing. Maurie Markman, MD: We talked about BRCA mutations, which it is increasingly understood that getting testing for BRCA1, BRCA2 is highly relevant. Key opinion leaders discuss the importance of HRD testing, with special consideration of tissue testing versus somatic testing.