Platinum Monotherapy Particularly Active in BRCA1/2-Mutant Metastatic Triple-Negative Breast Cancer
In the phase II TBCRC009 trial reported in the Journal of Clinical Oncology, Isakoff et al found that platinum monotherapy was active in treatment of metastatic triple-negative breast cancer, particularly in cases with BRCA1/2 mutation, and that an assay of genomic instability characteristic of BRCA1/2 deficiency may predict better outcome in patients without BRCA1/2 mutation.
In the study, 86 patients with metastatic triple-negative breast cancer received first-line (n = 69) or second-line physician’s choice of cisplatin (75 mg/m2, n = 43) or carboplatin (area under the curve = 6, n = 43) once every 3 weeks.
Response Rates
Among all patients, the response rate was 25.6% (95% confidence interval = 16.8%–36%), including rates of 32.6% with cisplatin and 18.7% with carboplatin. The response rate was 54.5% in 11 patients with identified BRCA1/2 mutations vs 19.7% in 66 without (P = .022).
HRD-LOH/HRD-LST Analysis
Analysis in 32 patients without BRCA1/2 mutation showed that patients with response had higher homologous recombination deficiency–loss of heterozygosity/homologous recombination deficiency–large-scale state transitions (HRD-LOH/HRD-LST) tumor assay scores (mean, 12.68 vs 5.11; P = .0318). Analysis of p63/p73 expression status in 61 patients, p53 and PIK3CA mutation status in 53, and PAM50 gene expression subtype in 55 showed no significant associations with response.
Six responders remained alive at a median of 4.5 years with no progression and no current treatment. None of five evaluated had BRCA1/2 mutations, with two having increased tumor HRD-LOH/HRD-LST scores.
The investigators concluded: “Platinum agents are active in [metastatic triple-negative breast cancer], especially in patients with germline BRCA1/2 mutations. A measure of tumor DNA repair function may identify patients without mutations who could benefit from platinum therapy agents. Prospective controlled confirmatory trials are warranted.”
Steven J. Isakoff, MD, PhD, of Massachusetts General Hospital, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by The Translational Breast Cancer Research Consortium, National Cancer Institute-AVON Partners for Progress, Golfers Against Cancer, Tracey Davis Breast Cancer Research Fund, Clinical Investigator Training Program of Harvard-Massachusetts Institute of Technology Health Sciences and Technology, and Dana-Farber/Harvard Cancer Center Tumor Imaging Metrics Core.
For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
