PracticeUpdate Oncology February 2019

SABCS 2018 27

Regional Analysis of Talazoparib for Treatment of Advanced Breast Cancer With Germline BRCA 1/2Mutation Interview with Jennifer Litton MD by Farzanna S. Haffizulla MD, FACP, FAMWA Dr. Haffizulla: There's regional analysis of the EMBRACA trial being presented this year. Can you remind us a little bit about the design of this particular trial and any important findings that have been published? Dr. Litton: Absolutely, so the EMBRACA trial was an international trial looking at tala- zoparib, which is a once-daily pill that’s a PARP inhibitor. It was an open label, two to one, randomized trial comparing it to physician’s choice of chemotherapy. At this point, it’s capecitabine, and vinorelbine, and gemcitabine, and eribulin. Really what we found is, it met its primary endpoint of progression-free survival with a hazard ratio of 0.54, which was statistically significant. Now, this was the second trial looking at PARP inhibitors in this group of women who had metastatic breast cancer, and who had a known germline BRCA mutation, so I think that we have definite proof that PARP inhibitors do have a role, especially in these women. This trial, as opposed to the OlympiA trial, was a little bit bigger and it was powered to look at overall survival, and when the trial was presented at the San Antonio con- ference in 2017, the overall survival data was immature with only 51% of the projected events at that time. We started to really see a separation of the curve at the end. It wasn’t statistically significant yet, but I hope to update you all soon as we get, as that data matures. The other thing that I think is very significant about the EMBRACA trial and the OlympiA trial, is that the quality of life was significantly improved. When we looked at quality of life measures, and compared talazoparib to physician’s choice of chemotherapy, the patients felt better. They had a better quality of life versus a decrease in quality of life that we saw in chemotherapy. We also saw a clinically mean- ingful decrease in the time to health deterioration compared to physician’s choice of chemotherapy, so we have an oral agent now, a once-a-day pill, that patients felt better compared to standard of care chemotherapy. Dr. Haffizulla: That’s excellent. Well, can you touch on any differences in toxicity lev- els that were observed? Dr. Litton: Sure, so when we looked at toxicity, the major toxicity was anemia, across the board, and that is what we see with this class of drugs, but this is usually very eas- ily managed with either dose delays then dose reductions, as well as transfusions, if needed. Outside of the hematologic toxicities really, they were mostly grade 1 and grade 2. Fatigue, and some grade 1 nausea and alopecia, were what we were seeing, but most of the alopecia was grade 1, and we were looking for it, asking for it, as well. Dr. Haffizulla: Any regional differences that were seen for trials such as this one? Dr. Litton: Right. You know, with this drug, an oral agent, we really wanted to make sure, as this was an international trial, were we seeing efficacy throughout, and we abso- lutely were, and I think that this is a good option for patients with metastatic breast cancer and a germline BRCA mutation. Dr. Haffizulla: Why do you think there were certain differences in different regions? Just from your own opinion, why do you, what accounts for that in your thoughts? Dr. Litton: You know, I think when you start to look at dissecting the data on unplanned things, I wouldn’t start to make any major conclusions based on that. What I would do is, kind of look at the overall showing. That we’re showing efficacy throughout. If there’s small differences throughout, that’s just the number of patients, and I think that if we really wanted to dive down and look at that, then we should construct the right trial to look at that, that’s powered to do so. I would just look at this more of a proof of principle that we are seeing activity throughout. Go to www.practiceupdate.com/c/77344 to watch this interview with Dr. Litton.

looking at the earlier breast cancer settings, either before surgery like we just discussed. And the OlympiA trial is looking at olaparib in the adjuvant setting. Dr. Haffizulla: Prior to this particular study that you just described so very eloquently to us, was there any other data that existed that shows the use of talazoparib in the new adjuvant setting? Dr. Litton: No. In fact, there’s been no other trial looking at just a single-agent PARP inhibitor in this setting. It really was novel. There have been other trials, including the I-SPY trial that looked at veliparib, but com- bined it with chemotherapy and went into the BrighTNess trial. There’s now multiple trials looking at this, but this was really the first time a single, oral, targeted therapy achieved pathologic complete response in triple-negative [breast cancer]. Now, not everyone responded; not everyone got that same outcome. To really look at that, we did ask patients who were, just partici- pated and really, especially this community, really wanted to learn as much as possible. We did biopsies pre and post. We drew blood, and what we also did is, built mouse models with the human breast tissue so that we can continue to learn from those that responded really well, and maybe we can do less, less chemo, and why did the people not respond as well, so that we can understand where the pathways that maybe we need target together.

Go to www.practiceupdate.com/c/77343 to watch this interview with Dr. Litton.

VOL. 3 • NO. 1 • 2019