Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Aug 14;10(1):73.
doi: 10.1038/s41523-024-00676-w.

Dose dense versus 3 weekly AC during neoadjuvant chemoimmunotherapy for triple negative breast cancer

Renata Colombo Bonadio  1   2 , Isadora Martins de Sousa  3 , Flávia Cavalcanti Balint  3 , Ana Carolina Marin Comini  3 , Monique Celeste Tavares  3 , Fernanda Madasi  4 , Jose Bines  2   4 , Rafael Dal Ponte Ferreira  5 , Daniela Dornelles Rosa  2   5 , Candice Lima Santos  6 , Zenaide Silva de Souza  7 , Daniele Assad-Suzuki  2   7 , Júlio Antônio Pereira de Araújo  2   8 , Débora de Melo Gagliato  2   8 , Carlos Henrique Dos Anjos  2   9 , Bruna M Zucchetti  2   10 , Anezka Ferrari  11 , Mayana Lopes de Brito  2   12 , Renata Cangussu  2   13 , Maria Marcela Fernandes Monteiro  14 , Paulo M Hoff  1 , Laura Testa  1   2 , Romualdo Barroso-Sousa  15   16
Affiliations

Dose dense versus 3 weekly AC during neoadjuvant chemoimmunotherapy for triple negative breast cancer

Renata Colombo Bonadio et al. NPJ Breast Cancer. .

Abstract

Neoadjuvant pembrolizumab plus chemotherapy (P + CT) has emerged as a standard of care for stage II-III triple-negative breast cancer (TNBC). However, the best anthracycline-cyclophosphamide (AC) schedule remains to be determined. While the KEYNOTE-522 regimen employs AC every 3 weeks (q3w AC), previous studies have shown overall survival benefits of dose-dense regimens for early-stage breast cancer. The Neo-Real study (GBECAM-0123) is a real-world data effort evaluating patients with TNBC treated with neoadjuvant P + CT in ten cancer centers since July 2020. The objective of this analysis was to evaluate the effectiveness and safety of dose-dense AC (ddAC) versus q3w AC. Among 333 patients included until November 2023, 311 completed neoadjuvant therapy and 279 underwent surgery with pathology reports available; ddAC was used in 58.2% and q3w AC in 41.8% of the cases. Most patients (69.1%) had stage II TNBC. A pCR was observed in 65.4% with ddAC and 58.7% with q3w AC (P = 0.260), while RCB 0-1 occurred in 82.4% and 73.5%, respectively (P = 0.115). Patients with stage III disease had a numerically higher pCR with ddAC (59% vs 40%, P = 0.155), while pCR rates were similar regardless of AC regimen in stage II disease (66.6% vs 64.5%; P = 0.760). While no significant disparities in drug discontinuation was noted, ddAC showed a trend towards higher rates of grade ≥3 AE (40.5% vs. 30.7%, P = 0.092). The Neo-Real study could not rule out a difference between ddAC and q3w AC during neoadjuvant P + CT. The observation of a potentially higher pCR with ddAC in stage III disease warrants further investigation.

PubMed Disclaimer

Conflict of interest statement

The Authors declare no Competing Non-Financial Interests but the following Competing Financial Interests: R.C.B.: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo, Nestle Health Science, Addium, Gilead, MSD, BMS, AstraZeneca, Ache, Pfizer. Financial support for educational programs and symposia: AstraZeneca, Daiichi-Sankyo, MSD. Institutional Research grant: Novartis, AstraZeneca. J.B.: Speaker fees and/or honoraria for consulting or advisory functions: AstraZeneca, Daiichi-Sankyo, Lilly, Gilead, Pfizer, Novartis, MSD, Roche, Knight Pharmaceuticals. Financial support for educational programs and symposia: Roche, Daiichi-Sankyo. D.D.R.: Speaker fees and/or honoraria for consulting or advisory functions: AstraZeneca, Daiichi-Sankyo, Lilly, Libbs, Pfizer, Novartis, Roche, GSK, Sanofi, Amgen, Zodiac Pharma. Financial support for educational programs and symposia: Roche. D.A.S.: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo. Financial support for educational programs and symposia: AstraZeneca. J.A.P.A.: Speaker fees and/or honoraria for consulting or advisory functions: Novartis, AstraZeneca, MSD, Lilly. D.M.G.: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo, Teva, Roche, AstraZeneca, Pfizer, Lilly, Novartis. Financial support for educational programs and symposia: AstraZeneca, Libbs, Roche. Research grant: Novartis. B.M.Z.: AstraZeneca, Daiichi-Sankyo, Eli Lilly, Gilead, Pfizer, Novartis, MSD, Roche, Addium. A.F.: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo, Novartis, Gilead, MSD, BMS, AstraZeneca, Pfizer. Financial support for educational programs and symposia: AstraZeneca, Daiichi-Sankyo, MSD, Novartis. C.H.A.: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo, Gilead AstraZeneca, Novartis, MSD. Financial support for educational programs and symposia: AstraZeneca, Daiichi-Sankyo, MSD, Lilly, Rcohe, Novartis, Gilead, Medscape. R.C.: Speaker fees and/or honoraria for consulting or advisory functions: AstraZeneca, Daichii-Sankyo, Eli Lilly, Gilead, MSD, and GSK. M.M.F.M.: Speaker fees and/or honoraria for consulting or advisory functions: AstraZeneca, Daiichi-Sankyo, Eli Lilly, Gilead, Adium, Novartis, MSD, and Roche. Financial support for educational programs and symposia: AstraZeneca, Daiichi-Sankyo, Gilead, Eli Lilly, Roche, MSD and Novartis. P.M.H.: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo. L.T.: Speaker fees and/or honoraria for consulting or advisory functions: Daiichi-Sankyo, MSD, AstraZeneca, Pfizer, Lilly, Novartis. Financial support for educational programs and symposia: AstraZeneca, Roche, Gilead. Institutional Research grant: Novartis. R.B.S.: Speaker fees and/or honoraria for consulting or advisory functions: AstraZeneca, Daiichi-Sankyo, Eli Lilly, Gilead, Libbs, Pfizer, Novartis, MSD, and Roche. Financial support for educational programs and symposia: AstraZeneca, Daiichi-Sankyo, Gilead, Eli Lilly, and MSD. Institutional Research grant: AstraZeneca, Daiichi-Sankyo. I.M.S., F.C.B., A.C.M.C., M.C.T., F.M., R.P.F., C.L.S., and Z.S.S. declare no conflict of interest.

Figures

Fig. 1
Fig. 1. Pathological complete response in the overall cohort and by disease stage according to AC regimen.
pCR pathologic complete response, ddAC dose-dense AC, q3w AC every 3-week AC.
Fig. 2
Fig. 2. Residual cancer burden (RCB) 0-1 in the overall cohort and by disease stage according to AC regimen.
RCB residual cancer burden, ddAC dose-dense AC, q3w AC every 3-week AC.
See this image and copyright information in PMC

References

    1. Schmid, P., Dent, R. & O’Shaughnessy, J. Pembrolizumab for early triple-negative breast cancer. N. Engl. J. Med.382, e108 (2020). 10.1056/NEJMoa1910549 - DOI - PubMed
    1. Schmid, P. et al. Event-free survival with pembrolizumab in early triple-negative breast cancer. N. Engl. J. Med.386, 556–567 (2022). 10.1056/NEJMoa2112651 - DOI - PubMed
    1. Schmid, P. et al. Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for early-stage triple-negative breast cancer: updated event-free survival results from the phase 3 KEYNOTE-522 study. Presented at the 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio; 2023. p. abstract LBO1-01.
    1. Mittendorf, E. et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomised, double-blind, phase 3 trial. Lancet (Lond., Engl.)396, 1090–1100 (2020).10.1016/S0140-6736(20)31953-X - DOI - PubMed
    1. Gianni, L. et al. Pathologic complete response (pCR) to neoadjuvant treatment with or without atezolizumab in triple-negative, early high-risk and locally advanced breast cancer: NeoTRIP Michelangelo randomized study. Ann. Oncol.33, 534–543 (2022). 10.1016/j.annonc.2022.02.004 - DOI - PubMed

LinkOut - more resources