Hope S. Rugo, MD: Priyanka, do you want to comment a little bit on how we're testing patients who have already had CDK4/6 [cyclin-dependent kinases 4 and 6] inhibitors versus not in the SOLAR-1 trial and then next steps?

Priyanka Sharma, MD: One of the things that always happens in our field is that new drugs and data come along, but where we put it in our patients in clinic today doesn't match the trial design. In SOLAR-1, the majority of patients did not receive a CDK4/6 inhibitor in the first-line setting with aromatase inhibitors, which would be considered current standard of care. And we're applying alpelisib to the second-line setting. We need studies that mimic the population that we're treating in clinic, and I believe one of the trials is looking at CDK4/6 inhibitor progression and the efficacy of PI3 kinase [phosphatidylinositol 3-kinase] inhibitors.

In my practice, I'm testing for PIK3CA mutations early on in the first-line setting on a CDK4/6 inhibitor just because as we know it's a fairly conservative mutation, so I'd rather have that information available when I need to make this change. But we do need the data of how efficacious this combination is when patients have received contemporary first-line endocrine therapy plus targeted therapy.

Hope S. Rugo, MD: We're really looking forward to the data from the BYLieve trial to try to help us understand benefits, although it's a single arm trial in patients with PIK3CA mutations who've had CDK4/6 inhibitors. There is one other question that's probably of interest to our audience and to all of us. John, if a patient has had ctDNA [circulating tumor DNA] testing and you don't find a PIK3CA mutation, how do the payers approach them getting NGS [next-generation sequencing] from the tissue?

John Fox, MD, MHA: Your question is if they do a circulating tumor DNA and don't find a PIK3CA mutation, would we pay for a repeat tissue biopsy and a solid tissue? I know that's an issue, but I think the important thing there, at least in my understanding, is to test people with circulating tumor DNA when they're progressing. If there is no evidence of progression, there may not be circulating tumor DNA being sloughed into the blood stream for sampling. But if the guidelines indicate that a patient might be appropriate for a therapy and the only way to get that would be through a repeat biopsy, we’d pay for it. I think the big question though is how many markers do you need to look at?

If you just need 1 marker, it could be a single gene test as opposed to next-generation sequencing where you're sequencing hundreds of different genes. The other time that we would pay for a next-generation sequencing panel, whether it be through ctDNA or through a tissue biopsy in solid tissue, would be if a patient was eligible for a clinical trial. Payers differ there. Certainly Medicare would cover a test in that situation, and they would certainly cover the clinical trials. Not all payers cover testing to determine whether patients are appropriate for a clinical trial. But we’ve said if we're going to cover a trial, we need to cover the tests that are appropriate to determine whether a patient is eligible.

Hope S. Rugo, MD: I think that's a good summary of what we are thinking about and what the payers are thinking about on both sides in terms of what you can do. You mentioned single gene testing on tumor tissue. We generally only get that when we send it to a sponsor rather than when we send it on our own. Claudine, have you sent single gene testing?

Claudine J. Isaacs, MD: I tried, and maybe the last time I tried was about 6 months ago, so I recognize the world changes. But I couldn't get single gene testing—it’s hundreds of genes or nothing when you’re sending off this next-generation sequencing.

Hope S. Rugo, MD: I think that cost relatively is similar for some of our sponsors in terms of our partners in the laboratory testing area. The cost is relatively similar to getting 1 gene versus many actually.

John Fox, MD, MHA: Well, in fact, the cost of the testing itself compared to the cost of these drugs—I try not to remember the cost of the drugs—but the CDK4/6 inhibitors are $10,000 or more a month, so the cost of single test, either circulating or solid tissue, is on the order of $2400 or $3000. It pales in comparison to the additive cost of treating the patient month over month with an expensive therapy, so it's a good investment to make to make sure that the patient is appropriate for a given therapy.

Hope S. Rugo, MD: Great. Thanks very much for your participation in this discussion. It was really interesting, and I think is an area that is changing on an ongoing basis. It'll be interesting to see what happens in the next year with more data.

Transcript Edited for Clarity