Tiffany Traina, MD: I think this is exciting data. OlympiAD was a randomized phase III trial of almost 300 women who were germline BRCA mutation carriers. This is based on central testing. They were women who had fewer than 2 prior lines of chemotherapy. A key point here (as we’ve been talking about platinum therapies) is that a portion of these women had prior exposure to a platinum but could not have progressed on platinum-based chemotherapy. So these women were randomized to either single-agent olaparib or treatment of physician’s choice, which was based on a reasonable list of standard drugs that we use for metastatic breast cancer, excluding a platinum. So there was no platinum-based therapy in that control arm.

The primary endpoint was median progression-free survival. The trial robustly met its primary endpoint. The progression-free survival improved from about 4 months to 7 months. This was about a 42% or 48% improvement in progression-free survival. Other efficacy endpoints—there was a doubling of response rate, from 30% to about 60%, favoring olaparib. Again, this is a single-agent oral therapy for patients.

In terms of toxicity, olaparib, as a single agent, was really relatively well tolerated. There was some hematologic toxicity with a bit of anemia, which I think was no surprise to folks based on the phase II experiences. There was also a bit of nausea and vomiting. When you looked at how that compared with treatment of physician’s choice with chemotherapy, the discontinuation from therapy due to adverse events was lower with olaparib than it was with standard chemotherapy. And it was rather uncommon.

The study actually looked at quality-of-life endpoints as well. Something that was very reassuring was that the time to a deterioration in quality of life was prolonged with olaparib over chemotherapy. So I think we have encouraging efficacy data. The study met its primary endpoint. There was also a nice tolerability profile and an improvement in quality of life.

Joyce O’Shaughnessy, MD: It made its way right into the New England Journal of Medicine and then right to FDA approval. What is the impact on our standard practice? Is it going to be a game changer for the germline BRCA patients?

Tiffany Traina, MD: There are a few things that I took away from these data. Number 1 is how critically important it is to know a patient’s germline BRCA status. We talked about the NCCN [National Comprehensive Cancer Network] guidelines. This is really a reminder to make sure that we’re not missing patients who could have the opportunity to have access to this treatment. We then divide out, by biology, what we’re doing in the triple-negative setting and what we’re doing in the ER-positive setting. These patients were HER2 normal. So that’s a separate category altogether.

I think it’s a wonderful opportunity for patients with germline BRCA mutations in triple-negative breast cancer. We saw an improved progression-free survival with an agent that was so well tolerated. It was oral. There was no alopecia associated with it. It’s really a win, and I think it moves this up to be a first-line opportunity for patients.

In the ER-positive setting, again, compared with chemotherapy, this was superior. I still think this would be sequenced at some point following endocrine therapy. I’d be happy to offer olaparib over chemotherapy. We all know when, clinically, we’re making that transition from an endocrine approach to a chemotherapy approach. I see olaparib moving in earlier for our patients with germline mutations.

Transcript Edited for Clarity