TY - JOUR
T1 - High-dose alkylating chemotherapy in BRCA-altered triple-negative breast cancer
T2 - the randomized phase III NeoTN trial
AU - Vliek, Sonja
AU - Hilbers, Florentine S
AU - van Werkhoven, Erik
AU - Mandjes, Ingrid
AU - Kessels, Rob
AU - Kleiterp, Sieta
AU - Lips, Esther H
AU - Mulder, Lennart
AU - Kayembe, Mutamba T
AU - Loo, Claudette E
AU - Russell, Nicola S
AU - Vrancken Peeters, Marie-Jeanne T F D
AU - Holtkamp, Marjo J
AU - Schot, Margaret
AU - Baars, Joke W
AU - Honkoop, Aafke H
AU - Vulink, Annelie J E
AU - Imholz, Alex L T
AU - Vrijaldenhoven, Suzan
AU - van den Berkmortel, Franchette W P J
AU - Meerum Terwogt, Jetske M
AU - Schrama, Jolanda G
AU - Kuijer, Philomeen
AU - Kroep, Judith R
AU - van der Padt-Pruijsten, Annemieke
AU - Wesseling, Jelle
AU - Sonke, Gabe S
AU - Gilhuijs, Kenneth G A
AU - Jager, Agnes
AU - Nederlof, Petra
AU - Linn, Sabine C
N1 - Funding Information:
The authors would like to thank Sjoerd Rodenhuis for his dedication to the NeoTN study. In addition, we would like to thank the patients and their families for participating in this study and all staff of the participating centres for their effort and commitment. This study was supported by The Dutch Cancer Foundation (KWF-Kankerbestrijding) and by the Schumacher Kramer Foundation, Amsterdam. This research was also supported by an institutional grant of the Dutch Cancer Society and of the Dutch Ministry of Health, Welfare and Sport.
Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/12
Y1 - 2023/12
N2 - Exploratory analyses of high-dose alkylating chemotherapy trials have suggested that BRCA1 or BRCA2-pathway altered (BRCA-altered) breast cancer might be particularly sensitive to this type of treatment. In this study, patients with BRCA-altered tumors who had received three initial courses of dose-dense doxorubicin and cyclophosphamide (ddAC), were randomized between a fourth ddAC course followed by high-dose carboplatin-thiotepa-cyclophosphamide or conventional chemotherapy (initially ddAC only or ddAC-capecitabine/decetaxel [CD] depending on MRI response, after amendment ddAC-carboplatin/paclitaxel [CP] for everyone). The primary endpoint was the neoadjuvant response index (NRI). Secondary endpoints included recurrence-free survival (RFS) and overall survival (OS). In total, 122 patients were randomized. No difference in NRI-score distribution (p = 0.41) was found. A statistically non-significant RFS difference was found (HR 0.54; 95% CI 0.23–1.25; p = 0.15). Exploratory RFS analyses showed benefit in stage III (n = 35; HR 0.16; 95% CI 0.03–0.75), but not stage II (n = 86; HR 1.00; 95% CI 0.30–3.30) patients. For stage III, 4-year RFS was 46% (95% CI 24–87%), 71% (95% CI 48–100%) and 88% (95% CI 74–100%), for ddAC/ddAC-CD, ddAC-CP and high-dose chemotherapy, respectively. No significant differences were found between high-dose and conventional chemotherapy in stage II-III, triple-negative, BRCA-altered breast cancer patients. Further research is needed to establish if there are patients with stage III, triple negative BRCA-altered breast cancer for whom outcomes can be improved with high-dose alkylating chemotherapy or whether the current standard neoadjuvant therapy including carboplatin and an immune checkpoint inhibitor is sufficient. Trial Registration: NCT01057069.
AB - Exploratory analyses of high-dose alkylating chemotherapy trials have suggested that BRCA1 or BRCA2-pathway altered (BRCA-altered) breast cancer might be particularly sensitive to this type of treatment. In this study, patients with BRCA-altered tumors who had received three initial courses of dose-dense doxorubicin and cyclophosphamide (ddAC), were randomized between a fourth ddAC course followed by high-dose carboplatin-thiotepa-cyclophosphamide or conventional chemotherapy (initially ddAC only or ddAC-capecitabine/decetaxel [CD] depending on MRI response, after amendment ddAC-carboplatin/paclitaxel [CP] for everyone). The primary endpoint was the neoadjuvant response index (NRI). Secondary endpoints included recurrence-free survival (RFS) and overall survival (OS). In total, 122 patients were randomized. No difference in NRI-score distribution (p = 0.41) was found. A statistically non-significant RFS difference was found (HR 0.54; 95% CI 0.23–1.25; p = 0.15). Exploratory RFS analyses showed benefit in stage III (n = 35; HR 0.16; 95% CI 0.03–0.75), but not stage II (n = 86; HR 1.00; 95% CI 0.30–3.30) patients. For stage III, 4-year RFS was 46% (95% CI 24–87%), 71% (95% CI 48–100%) and 88% (95% CI 74–100%), for ddAC/ddAC-CD, ddAC-CP and high-dose chemotherapy, respectively. No significant differences were found between high-dose and conventional chemotherapy in stage II-III, triple-negative, BRCA-altered breast cancer patients. Further research is needed to establish if there are patients with stage III, triple negative BRCA-altered breast cancer for whom outcomes can be improved with high-dose alkylating chemotherapy or whether the current standard neoadjuvant therapy including carboplatin and an immune checkpoint inhibitor is sufficient. Trial Registration: NCT01057069.
UR - http://www.scopus.com/inward/record.url?scp=85170380516&partnerID=8YFLogxK
U2 - 10.1038/s41523-023-00580-9
DO - 10.1038/s41523-023-00580-9
M3 - Article
C2 - 37689749
AN - SCOPUS:85170380516
SN - 1526-8209
VL - 9
JO - npj Breast Cancer
JF - npj Breast Cancer
IS - 1
M1 - 75
ER -