Neoadjuvant Therapy Options in Triple-Negative Breast Cancer

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Transcript:

Hope S. Rugo, MD, FASCO: I think the next question is what would you do, Paolo? And what did you think about that platinum data?

Paolo Tarantino, MD: I totally agree that we have seen recent trials confirming the benefits of neoadjuvant platinum and several trials showing that neoadjuvant checkpoint blockade improves PCR [polymerase chain reaction] and some trials also showing EFS [event-free survival] data. So there was a major step forward in this very hard-to-treat disease. And I also agree that patients with the residual disease are a huge unmet need and I feel that there’s so much more to do because we know that we have capecitabine. Based on the CREATE-X trial, we can continue checkpoint inhibition, but these patients have already shown resistance to checkpoint inhibition in the adjuvant setting. And that’s where a class of drugs that we’re going to discuss probably in-depth, antibody-drug conjugates, I believe, and I hope that could be helpful, particularly since several of them have shown to be active in chemorefractory tumors in the advanced setting. And so, we hope that we can translate that into the post-neoadjuvant setting.

And there are a few trials that are really interesting, in my opinion, like the SASCIA trial of post-neoadjuvant sacituzumab govitecan [Trodelvy] for patients with residual disease after neoadjuvant treatment and also the OptimICE trial we look at the same question. And then there is another drug, too, not only sacituzumab govitecan but also datopotamab deruxtecan [Dato-DXd]and that’s shown interesting activity in the advanced setting and will be started in a randomized trial in the post-neoadjuvant setting. I believe it was the TROPION-Breast03 trial. So a lot going on in this space to try to improve the outcome for these patients that we know have a high risk of recurrence, but at the same time I feel that we need also biomarkers to adapt treatment, even upfront in the neoadjuvant setting because we know that now we give the KEYNOTE trial regimen. It’s an intense regimen and allows to improve outcomes.

But I would like to understand which patients require checkpoint inhibition, which might not require that, or which patients might be cured by less chemotherapy. And I feel that the biomarker that we always use in the advanced setting, PD-L1 expression really didn't help us here in the early setting and so I wanted your opinion based on this. Whereas, regarding carboplatin, I think right now there are so many trials that have shown consistent outcome improvement that now really, we should try for most of the patients to include carboplatin. And probably the hardest patients are the ones that are more elderly patients, more frail, where giving such an intense regimen might create challenges. But, at the same time, it would improve outcomes and so we should try to stick as much as possible to the KEYNOTE-522 trial regimen.

Transcript edited for clarity.