High-dose alkylating chemotherapy in BRCA-altered triple-negative breast cancer: the randomized phase III NeoTN trial

• Published in: NPJ breast cancer Vol. 9; no. 1; p. 75
• Main Authors: Vliek, Sonja, Hilbers, Florentine S., van Werkhoven, Erik, Mandjes, Ingrid, Kessels, Rob, Kleiterp, Sieta, Lips, Esther H., Mulder, Lennart, Kayembe, Mutamba T., Loo, Claudette E., Russell, Nicola S., Vrancken Peeters, Marie-Jeanne T. F. D., Holtkamp, Marjo J., Schot, Margaret, Baars, Joke W., Honkoop, Aafke H., Vulink, Annelie J. E., Imholz, Alex L. T., Vrijaldenhoven, Suzan, van den Berkmortel, Franchette W. P. J., Meerum Terwogt, Jetske M., Schrama, Jolanda G., Kuijer, Philomeen, Kroep, Judith R., van der Padt-Pruijsten, Annemieke, Wesseling, Jelle, Sonke, Gabe S., Gilhuijs, Kenneth G. A., Jager, Agnes, Nederlof, Petra, Linn, Sabine C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.09.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 692/4028/67/1059/99; 692/4028/67/1347; Biomedical and Life Sciences; Biomedicine; Breast cancer; Cancer Research; Cancer therapies; Cell Biology; Chemotherapy; Human Genetics; Oncology
• ISSN: 2374-4677; 2374-4677
• DOI: 10.1038/s41523-023-00580-9

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.