Case 4: PARP Inhibitors for Treating BRCA+ Triple-Negative Breast Cancer

Adam Brufsky, MD, PhD: The other big trial is EMBRACA, which included patients who had metastatic disease in the brain. They were randomized to the choice of chemotherapy—capecitabine, eribulin, gemcitabine, or vinorelbine—versus talazoparib. In this trial, there was a progression-free survival benefit.

Again, we saw a hazard ratio very similar to that of the OlympiAD trial with olaparib. There appeared to be at least glimmers of a survival benefit. Again, this is an interim analysis, so we need to see further data regarding whether there would be a benefit with talazoparib. Hopefully, when they do this additional survival analysis, they cut the data the same way that olaparib was cut for the patients who had not had prior chemotherapy. This is going to be really interesting and may potentially change our practice. Up front, I think a lot of us said, “Listen, if there’s no survival benefit we don’t really care.”

But if the patient really does have a survival benefit in the absence of getting chemotherapy, then I would really argue to give these agents before chemotherapy. And again, the safety is very similar. I think the unique adverse events are anemia and neutropenia, but they really weren’t bad. The instance of neutropenia was actually less than chemotherapy. It was grade 4.

Hope Rugo, MD, FASCO: That was great. It was an excellent review of what we’ve seen in the data with PARP inhibitors. It is so encouraging that we finally were able to get 2 drugs approved for patients with germline BRCA mutations in metastatic breast cancer.

Now I think the big question is, how do we incorporate the PARP inhibitors? As you recall, this is a patient who has metastatic disease with lung involvement but not a lot of symptoms in bone, and she has a tumor that is triple-negative but PD-L1 testing is 0. What treatment options would you consider for this patient, and how would you make a decision? Adam, do you want to start?

Adam Brufsky, MD, PhD: I think if the patient doesn’t have that many symptoms and really if that data does hold up from the analysis, she really should get a PARP first. I think that if there were a true survival benefit, people would get PARP up front.

Hope Rugo, MD, FASCO: Ian, how do you decide?

Ian Krop, MD, PhD: I think in this case, when the patient is PD-L1–negative, it’s pretty straightforward. You have randomized trials showing superior PFS [progression-free survival] versus chemotherapy, and they’re at least as well tolerated as chemotherapy for most patients. And you can avoid the infusion. I think for this patient, a PARP inhibitor is a very good choice. I think it gets more complicated for the PD-L1–positive patients with a BRCA mutation.

Hope Rugo, MD, FASCO: That is a really good point. We don’t know what to do, although there is a lot of interest in PARP inhibitors as maintenance. Studies will be looking at the overall triple-negative breast cancer population with immunotherapy and PARP inhibitors as combined treatment as maintenance after a chemotherapy/I-O [immuno-oncology] induction or even just chemotherapy induction.

That will be interesting because we’ll be able to look at the BRCA-mutation population in a subset analysis.

Transcript edited for clarity.