PracticeUpdate Oncology February 2019

CONFERENCE COVERAGE 26

Neoadjuvant Talazoparib for BRCA 1/2Mutated Triple- Negative Breast Cancer Interview with Jennifer Litton MD by Farzanna S. Haffizulla MD, FACP, FAMWA

Dr. Litton is Associate Professor in the Department of Breast Medical Oncology, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, Texas.

to see is what would happen if we gave 6 months and then took people to surgery because then we’d really know, was it just imaging or what was really there. So we did another expansion with just 6 months of talazo- parib and then surgery. What we found was a pathologic complete response rate of over 50%with just the pill, no chemo. Given that, and the toxicity profile, is nowmoving forward to this multi-center trial with 6 months of talaz- oparib, a once daily pill, no chemotherapy and then to surgery. Now, people can go on and get whatever after surgery. Chemo, if they need it, any other treatments that’s appropriate, but you know, I think this is an intrigu- ing way to start looking at these drugs when we have a real idea of who may benefit. Dr. Haffizulla: Well, that’s exciting, you know, at least laying it out in that sense. One pill, better quality of life and good outcomes that you’re seeing. What is a timeframe for completion of this particular study? Dr. Litton: It just started in opening accrual, so I’m hope- ful in the next 2 years we’ll complete it and be able to present those results on a bigger scale. Dr. Haffizulla: Can you talk about how talazoparib is being used now in this particular patient population? Dr. Litton: Right now, talazoparib is FDA approved for patients with metastatic breast cancer who have a known germline BRCA mutation. That’s the standard of care usage. It’s the second PARP inhibitor. Olaparib also received FDA approval for the exact same indica- tion; all within the last year. And I think really showing that this class of drugs has activity and a future for our patients. There’s a lot of trials going on looking at new combinations with the PARP inhibitors that might expand who could benefit or improve the duration of response in patients with metastatic [disease], and multiple trials

Dr. Haffizulla: You’re presenting on an ongoing trial on the use of talazoparib in the new adjuvant setting in patients with BRCA1 and -2 mutated triple-negative breast cancer. Canyou tell us a littlebit about thedesign of the study? Dr. Litton: Sure, so this study really stemmed off a pilot that we did at MDAnderson. First, talazoparib, it’s an oral PARP inhibitor given once daily, and had been tested in the metastatic setting. But when we see something, whether if this drug or any other drug that’s working well in that situation, we always try to see, can we bring it up earlier? Can we cure more people earlier? And given what we were seeing, I wanted to see, in some- one who hadn’t been treated, what it could do. So we started off with a really small pilot trial because initially people thought no one would go on a single pill, once a day, and delay chemo and worried about outcomes, which I think is very reasonable. So we started a pilot with just 2 months of talazoparib, and we were doing ultrasounds every month to make sure, and with the endpoints then, could we even accrue patients? Could we put 20 patients on in 2 years, and could we do it with acceptable toxicity and no grade 4 toxicities? But after a year, 13 patients went on the trial, and no grade 4 toxicities. But what was really astoundingwas that, when wewere followingwith the ultrasounds, themedian tumor volume decrease was 88%, with only 2 months of ther- apy, and we really felt that there was little chance that we wouldn’t meet that objective. And what we really wanted

" What was really astounding was that, when we were following with the ultrasounds, the median tumor volume decrease was 88%, with only 2 months of therapy, and we really felt that there was little chance that we wouldn’t meet that objective. " PRACTICEUPDATE ONCOLOGY