Dissemin is shutting down on January 1st, 2025

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Springer, Breast Cancer Research and Treatment, 1(207), p. 179-185, 2024

DOI: 10.1007/s10549-024-07354-2

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Assessment of efficacy and safety of dose-dense doxorubicin and cyclophosphamide (ddAC) in combination with immunotherapy in early-stage triple-negative breast cancer

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

Abstract Purpose This study aimed to assess safety and efficacy of a modified KEYNOTE 522 protocol, which incorporated pembrolizumab every 6 weeks, allowing for concomitant dose-dense (14 day) doxorubicin and cyclophosphamide (ddAC). By optimizing this dosing, the intention of this modified protocol was to improve pathologic complete response (pCR) rates in a population associated with a poorer prognosis. Methods This was a retrospective, single-center, cohort study. Patients were included if they had early stage, triple-negative breast cancer, and received at least one dose of AC. The entire cohort received neoadjuvant chemotherapy including weekly carboplatin and paclitaxel with pembrolizumab every 3 weeks for 12 weeks (4 cycles). The group then received either ddAC with pembrolizumab 400 mg every 6 weeks, or AC with pembrolizumab 200 mg every 3 weeks. The primary objective was pCR rate at time of surgery. Results This study assessed outcomes in 25 patients over 34 months. The pCR rate in the pembrolizumab, AC 3-week cohort was 64.3% versus 81.8% in the ddAC and 6-week pembrolizumab group. No pembrolizumab-associated grade 3–4 adverse events occurred in the either cohort. Despite seeing an increased incidence of grade 3–4 toxicities in the ddAC arm, this did not result in additional chemotherapy delays or dose reductions. Conclusion This study demonstrated tolerability and a potential for favorable outcomes with this patient population, making this modified KEYNOTE 522 protocol a reasonable treatment approach. Larger, prospective studies are warranted to assess the feasibility of this dosing and true optimization of patient outcomes given the small sample size of this study.