Medicine Matters oncology

Today we're going to talk about the NEOTALA study that was presented at the ASCO virtual annual meeting in 2021. The NEOTALA study first started as a small pilot trial at MD Anderson. It first started with two months of talazoparib, prior to standard chemotherapy, for patients with early stage breast cancer who had a germline BRCA mutation. And after accruing 13 patients to that study, we saw a dramatic response in patients with a median tumor volume decrease of 88%.

Given that, and the ease of taking a pill once a day versus polychemotherapy, we expanded the study for six months of talazoparib therapy then surgery. And what we found for patients with germline BRCA mutations that were HER2 normal or wild-type, was a significant pathologic complete response rate. And it was the first time we've ever seen a pathologic complete response to a single targeted agent in patients with triple negative breast cancer.

Given the simplicity of taking one pill a day, the trial went on to the NEOTALA study, which was a multi-center trial, single-arm phase II. And it accrued patients, specifically started with patients with only triple negative breast cancer. Although at the end of the trial, the conclusions were amended to include ER positive patients. The study closed to its accrual, prior to having an ER positive patient accrue to the study.

The study was very similar, it was six months of neoadjuvant, talazoparib, a PARP inhibitor, followed by surgery, and then physician's choice of chemotherapy. There was an independent central review of the pathology by Dr. Fraser Symmans from MD Anderson. And what was found was by the independent central review, there was a pathologic complete response rate of 45.8% and 49.2% in the intention to treat population. If we look by the investigator, it was 45.8% in the evaluable, and 47.5% in the intention to treat.

Now one thing about this study is that the first part of the trial, the sponsor made a business decision to decrease the planned accrual. So it was originally planned for about over 120 patients, it was decreased to 61 patients, and when the trial reached 61 patients it was closed. The biostatistical plan was for PCR rate to exceed 45% with a 0.8 but the posterior probability in this trial was 0.55.

When we look at toxicities, the toxicities are what we see with PARP inhibitors. So fatigue, nausea, and specifically with talazoparib, alopecia, which we don't see as much with the other PARP inhibitors. But anemia is often the dose limiting toxicity. And 11 out of 61 patients had some treatment emergent SAE, and grade 3 anemia was the most common. 33% had dose interruptions, 39% dose reductions, and 33% had transfusions due to their adverse events.

So this trial showed, in a multicenter fashion, that patients who took a single agent pill once a day did have a pathologic complete response rate of 45.8 by the independent reviewer in the evaluable, a 49.2 in the intention to treat. It is comparable to those observed with a combination anthracycline and taxane chemotherapy regimens. I think there's definitely more work to be done in this to decrease the exposure to chemotherapy, the simplicity of the treatment.

Certainly the adverse event of anemia, continues to be an issue with this class of drugs. I also think it'll be interesting to see how this moves forward with patients with hormone receptor positive breast cancer, as these are the patients that I think a lot of people feel much more comfortable decreasing the use of polychemotherapy after, given the strong efficacy of aromatase inhibitors in ovarian suppression, and tamoxifen in this group as well. Thank you very much.