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Carboplatin improved outcomes in patients with BRCA1/2-mutated metastatic breast cancer

SAN ANTONIO — Patients with metastatic breast cancer who harbored BRCA1 or BRCA2 mutations achieved superior response rates and PFS when they received carboplatin vs. docetaxel chemotherapy, according to phase 3 study results presented at the San Antonio Breast Cancer Symposium.

Carboplatin and docetaxel were associated with comparable outcomes in the total study cohort of triple-negative or BRCA-mutated breast cancers; however, docetaxel appeared to be more effective among patients with non–basal-like disease.

“Triple-negative breast cancer is a heterogeneous disease, but distinct subsets are recognized,” Andrew Tutt, PhD, of Kings College in London, said during a presentation. “BRCA1/2 mutation-associated and some triple-negative breast cancers share impaired homologous recombination repair mechanisms conferring sensitivity to platinums in both preclinical and clinical datasets, but no study has directly compared single-agent platinum chemotherapy with standard of care and mechanistically distinct taxanes in these populations of metastatic breast cancer patients.”

Tutt and colleagues evaluated data from 376 patients who had triple-negative breast cancer or who had a known BRCA mutation (8%). A majority of patients (91%) had metastatic disease, and 9% and locally advanced disease. Thirty-four percent of patients had been treated with prior taxane therapy.

Genotyping analyses identified additional patients with BRCA mutations, for a total population of 43 BRCA mutation carriers.

Researchers randomly assigned patients 1:1 to receive carboplatin (area under the curve 6) or 100 mg/m2 docetaxel every 3 weeks for six to eight cycles.  A majority of patients in both arms achieved a dose intensity ≥85% (carboplatin, 72.9%; docetaxel, 72.3%).

Median follow-up was 11 months (interquartile range, 6.5-16.9).

In the overall population, the primary endpoint of objective response was not statistically different between patients who received carboplatin vs. docetaxel (31.4% vs. 35.6%; absolute difference -4.2%; 95% CI, -13.7 to 5.3).

Median PFS was 3.1 months in the carboplatin arm and 4.5 months in the docetaxel arm (absolute difference, -0.4; 95% CI, -1.1 to 0.3). OS also was similar between the arms (carboplatin, 12.4 months; docetaxel, 12.3 months; absolute difference, -0.2; 95%CI, -1.1 to 0.8).

However, significantly more patients who harbored BRCA1/2 mutations responded to carboplatin vs. docetaxel (68% vs. 33.3%; P=.03). Response rates did not significantly differ among BRCA-negative patients (28.2% vs. 36.6%; P=.16).

Researchers also evaluated response according to impaired homologous recombination repaired mechanism (HRD). However, response rates did not significantly differ among patients with high or low HRD scores.

Among other subtypes, only patients with non-basal disease demonstrated statistically different response rates. Significantly more of these patients responded with docetaxel than carboplatin (73.7% vs. 16.7%; P<0.01).

The safety profile in both arms was consistent with previous data. Significantly more patients who received docetaxel experienced febrile neutropenia and neuropathy (P˂.01 for both).

“This trial provides no evidence of superior response of carboplatin compared to paclitaxel in unselected triple-negative breast cancer,” Tutt said. “Patients with BRCA1 and BRCA2 mutations experienced significantly greater response and PFS with carboplatin than docetaxel. The results support BRCA1/2 genotyping to inform therapy choice in metastatic triple-negative and familial breast cancer.”

For more information:

Tutt A. Abstract #S3-01. Presented at: San Antonio Breast Cancer Symposium; Dec. 9-13, 2014; San Antonio.

Disclosure: Researchers report advisory board roles with and honoraria from Amgen, AstraZeneca, Eisa, GlaxoSmithKline and Novartis.

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