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Dr Brufsky Discusses Evolving Strategies in Early-Stage TNBC Treatment

 

Adam M. Brufsky, MD, PhD, University of Pittsburgh School of Medicine, Magee-Women’s Cancer Program, Comprehensive Breast Cancer Center, UPMC Hillman Cancer Center, discusses evolving strategies in neoadjuvant/adjuvant treatment of early-stage triple-negative breast cancer (TNBC).

These data were presented at the 2021 Miami Breast Cancer Conference. 

 

Transcript

Hello, name is Adam Brufsky. I am a medical oncologist in Pittsburgh, Pennsylvania. I am a professor of medicine at the University of Pittsburgh. I am co-director of the comprehensive breast cancer center there and associate chief of the division of hematology oncology at the UPMC Hillman Cancer Center here at the University of Pittsburgh.

At Miami Breast this year, I am talking about evolving strategies in the treatment of triple-negative breast cancer, particularly adjuvant treatment of triple-negative breast cancer.

I think that it is an important issue in that probably at least 30-40% of women with triple-negative disease in the adjuvant setting will relapse with distant disease, often very quickly after their initial therapy for early-stage breast cancer.

We have really thought very long and hard over the years- we, being the medical community interested in breast cancer- about what is going on. I think a lot of us are beginning to realize that triple-negative breast cancer in particular could be a disease of the immune response to breast cancer.

That is it tends to occur in younger women. It is not as estrogen-driven as some of the other cancers, and it could be that there just may be ways that this cancer avoids the immune system. For that reason, there has been an enormous amount of interest in immune checkpoint inhibitors, among other therapies, to try to modulate disease.

We have a number of clinical trials that have been presented over the last few years that I will be talking, and that I have talked about, in the presentation at Miami Breast, in particular, KEYNOTE-522, which was a trial of adriamycin and cytoxan with carboplatin and paclitaxel with or without adjuvant pembrolizumab that was given concomitantly, and then for a year after.

In that trial, initially, there were substantial differences in PCR rates. A PCR rate as high of almost 70%, I think 77%, in women who has PD-1, L1-positive disease with getting pembrolizumab and their chemotherapy.

What was very interesting in that trial, actually, was that women in the control arm who had PD-1, L1-positive disease also had a superior pathological complete response rate of about 45-50%, versus about 30-35% in the control arm.

There is something not only about getting potentially the checkpoint inhibitor, but actually having PD-1, L1-positive that could have been due to immune infiltration, whatever, but this is really important.

There are other trials that were done with other checkpoint inhibitors, IMpassion031, also a trial presented in the last year, demonstrated the superiority of a checkpoint inhibitor -- in this case, atezolizumab -- adding to chemotherapy in the neoadjuvant study with a higher PCR rate.

Indeed, a trend also toward improved event-free survival. There are at least two trials, and there are others that I've talked about in the presentation, suggesting that checkpoint inhibitors could be a benefit. What was interesting, however, in the last several weeks, the US FDA had an oncology drugs advisory committee meet to discuss the KEYNOTE-522 data.

What was very interesting was that there were three interim analyses. In the third interim analysis, the difference in PCR rates between the group that had checkpoint inhibitors in KEYNOTE-522 versus the group that didn't was only 7.5%, where it had started, I think, a lot higher, like in the 15-20% range.

This was concerning to the FDA, and they were also a little bit concerned that the event-free survival was a little short. The follow-up was only about 13-15 months. I think the ODAC actually voted 10-nothing to await further data, await further events-free survival data, before making a final determination.

While I think these drugs do have an enormous amount of promise, and there was an ongoing trial, NCBB-59, which is adjuvant chemotherapy, or neoadjuvant chemotherapy with or without atezolizumab - it is a larger version, in many ways, of IMpassion031 - while that is ongoing and is going to be very, very important confirmatory data for all these trials...

While we await that data, while we await the continuation data of KEYNOTE-522, it is going to be a really interesting question for all of us to try to determine whether we should be using checkpoint inhibitors at this point in practice.

They are clearly not FDA-approved, and I think that how we decide to deal with this while we await FDA approval, clearly, the book answer is that we do not use them. On the other hand, I think that oncologists worldwide who treat breast cancer will be considering these data very carefully.

That essentially is the gist of the presentation I'm giving at Miami Breast, and I welcome you to see it. Again, thank you very much.

 

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