DR LOVE: Getting back to your patient with the triple-negative disease, she gets neoadjuvant therapy and then unfortunately develops metastatic disease. And I see that she actually entered a trial of a PARP inhibitor. Which PARP inhibitor? And what happened?

DR HURVITZ: She went on the EMBRACA study, which is a Phase III clinical trial looking at talazoparib. And this is a potent PARP inhibitor. There’s a lot of excitement around it.

But it is arguably one of the most potent, if not the most potent, PARP inhibitor. So this is a single-agent PARP inhibitor compared to treatment of physician’s choice. And control-arm patients have choices of chemotherapy.

She went on this study, and she had a very good response. The cervical and supraclavicular lymph node disappeared. Her lung metastasis shrunk. Did well through 2 scans and, around month 5 or 6, had progressive disease. And the issue was, we had to hold drug several times and dose reduce due to neutropenia.

So the drug’s got a lot of cytopenias associated with it, at least in the patients that I’ve treated. Talking now anecdotally, because we don’t have overall results of the study. But the cytopenia led to the dose reductions. And it’s caused me to wonder whether or not she would have done better had we been able to maintain her at a higher dose or do something to help support her and get her though it without the dose reductions.

DR LOVE: Now, just to clarify, did she have chemotherapy also or just this PARP inhibitor?

DR HURVITZ: Just the PARP inhibitor.

DR LOVE: And so this obviously looks like a clinically useful response. And that is a very common question we get from oncologists. You unfortunately, particularly in triple-negative disease, run out of options really fast. And you have olaparib out there, approved in ovarian cancer.

There are trials, obviously, looking at olaparib in every possible stage. What do we know right now about single-agent response rates to PARP inhibitors, including olaparib, in breast cancer?

DR HURVITZ: We’ve got early-phase clinical trials suggesting very good response rates. And with this particular drug, my colleague, Zev Wainberg presented Phase I data, and they had a breast cohort in there. And the response rates were quite good, on the order of over 40%. And I had a couple of patients on his study. And that generated in me a lot of excitement and enthusiasm about this particular molecule. But the cytopenias are something that have to be dealt with. There are a lot of questions surrounding whether we should be using these PARP inhibitors in combination with low-dose chemotherapy, which preclinically looks very promising. So I think we need to explore this a little bit further.

And then the unanswered question that everyone’s afraid to test clinically, given the debacle with the iniparib study, is whether or not PARP inhibitors would be effective in other forms of high-grade triple-negative or BRCA-like breast cancers. And that’s something that hopefully studies will be designed to address.

DR LOVE: So an oncologist emails you and says, “I’ve got this patient with triple-negative disease. We’ve given her chemotherapy. She’s got metastatic disease. She’s BRCA-positive. I want to give her olaparib.” Do you say, “Yes, good idea,” “bad idea” or in between?

DR HURVITZ: I’d say, “Can you find a clinical trial to put her on?” Have I used it off label? Yes. Have I seen much? No. I’ve done it a couple of times, usually very late stage, so I’m not sure it was a fair assessment of whether or not it’s effective in very late stage, a Hail Mary run. But yes, I know of clinicians that do this. And I think that it’s a reasonable thing to do, but I’d prefer to put a patient on a clinical trial and address it.

Genomic assays and (neo)adjuvant treatment decision-making

Early-stage breast cancer in the adjuvant and neoadjuvant settings

Management of metastatic breast cancer (mBC)

CDK4/6 inhibitors for the treatment of breast cancer

Checkpoint inhibitors and other novel immunotherapeutic approaches to breast cancer

Triple-negative and BRCA mutation-positive breast cancers