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BCC 2021 | Encouraging developments in triple negative breast cancer immunotherapy

Patients with triple negative breast cancer (TNBC) typically have a poor prognosis, reflecting high recurrence rates and treatment refractoriness. Recent advances in breast cancer immunology research have yielded potential new therapeutic strategies for this setting. Sherene Loi, MBBS, PhD, FRACP, FAHMS, Peter MacCallum Cancer Centre at the University of Melbourne, Melbourne, Australia, shares findings from the latest major trials of immune-targeting agents in early-stage TNBC. The Phase III KEYNOTE-522 (NCT03036488) trial of pembrolizumab plus chemotherapy, and the IMpassion031 trial (NCT03197935) of atezolizumab with chemotherapy have both produced evidence in favor of immune agents, but long-term outcome data is lacking. This interview took place during the 17th St. Gallen International Breast Cancer Conference.

Transcript (edited for clarity)

The largest study was the KEYNOTE-522 and that was presented a couple of years ago now. At the first interim analysis, which was around 600 patients, it was a study with over 1,000 patients so the largest Phase III study. It was a neoadjuvant and adjuvant phase. The pCR end point was reported and that did show that the addition of pembrolizumab increased the pCR rate, by a small amount, but it was significant...

The largest study was the KEYNOTE-522 and that was presented a couple of years ago now. At the first interim analysis, which was around 600 patients, it was a study with over 1,000 patients so the largest Phase III study. It was a neoadjuvant and adjuvant phase. The pCR end point was reported and that did show that the addition of pembrolizumab increased the pCR rate, by a small amount, but it was significant. We don’t know how clinically relevant that amount of will be, however, in the long term and that was why the FDA rejected the approval of pembrolizumab for this indication at the moment. We have the IMpassion031, which is a smaller study, over 300 patients, which again, looked at just the pCR end point. This used a little bit less heavy chemotherapy than the KEYNOTE-522 but again was statistically significant in that the pCR rate was improved.

So there’s two studies that are supportive of each other, but we won’t know how the long term outcome of that study for a while yet. And of course, it’s not powered to look at differences in the long term. A confirmatory study, a larger study is about to start using that combination. And then we have a scattering of smaller studies. Two of which was statistically significantly negative, but also did show a small increase in the pCR rate. So they’re are all kind of supportive that the addition of these agents do increase the pCR rate but I think we have to fine tune the population a little bit, probably the chemotherapy backbone, and we have to wait to see how this will pan out in the long term.

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Disclosures

Research funding to institution: Novartis, Bristol Meyers Squibb, Merck, Puma Biotechnology, Eli Lilly, Nektar Therapeutics Astra Zeneca, Roche-Genentech, Seattle Genetics.
Consultancy (not compensated): Seattle Genetics, Novartis, Bristol Meyers Squibb, Merck, AstraZeneca, Roche-Genentech.
Consultancy (paid to institution): Aduro Biotech, Novartis, GlaxoSmithKline, Roche-Genentech, Astra Zeneca, Silverback Therapeutics, G1 Therapeutics, PUMA Biotechnologies, Seattle Genetics, Bristol Meyers Squibb.
Scientific Advisory Board Member: Akamara Therapeutics.
Supported by the National Breast Cancer Foundation of Australia Endowed Chair and the Breast Cancer Research Foundation, New York.

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