SAN ANTONIO—Carboplatin is associated with better outcomes than docetaxel among women with BRCA1/2 mutation–harboring metastatic or recurrent locally advanced breast cancer, according to new findings from the randomized phase 3 TNT trial, presented at the 2014 San Antonio Breast Cancer Symposium.
“There was no evidence of superior response to carboplatin compared to docetaxel in unselected [triple-negative breast cancer] TNBC,” reported lead author Andrew Tutt, PhD, of Kings College London in London, England. But “patients with BRCA1 or BRCA2 mutation experience significantly greater response and progression-free survival with carboplatin than docetaxel.” The results support BRCA1/2 genotyping to inform treatment decisions in metastatic TNBC and familial breast cancers, he concluded.
“Subgroups within sporadic triple-negative breast cancers appear to share impaired DNA damage response mechanisms with BRCA1/2 mutation-associated breast cancers,” Dr. Tutt said. “This has been hypothesized to confer particular sensitivity to DNA-damaging platinum chemotherapy.” To test this hypothesis, the TNT trial team enrolled women with metastatic or recurrent locally advanced TNBC or BRCA1/2 mutation-associated breast cancer.
“Eligible patients had either ER-negative, PR-negative, or HER2-negative breast cancer or were known BRCA1/2 carriers (any ER/PR/HER2 status),” they explained. “Patients were randomized 1:1 to receive either carboplatin (C; AUC 6 every three weeks) or docetaxel (D; 100 mg/m2 every three weeks) for 6 cycles or until disease progression, if sooner.”
Patients were allowed to cross over to the other treatment group upon confirmed progression, Dr. Tutt noted. Excluded patients included those with ECOG performance status higher than 2, and those who had received adjuvant taxane treatment in the past 12 months or previous platinum chemotherapy treatment, or previous non-anthracycline chemotherapy for metastatic disease, Dr. Tutt reported.
A total of 376 evaluable patients were enrolledat 74 cancer centers in the United Kingdom. Of these, primary tumor tissue was available for 309 patients, blood samples for 288 patients, positive lymph node samples for 143 patients, and recurrent tumor tissue for 102, Dr. Tutt said.
Overall, at a median follow-up of 11.0 months, outcomes were similar between the treatment groups, he reported. Objective response, progression-free survival (PFS) and overall survival were not significantly different between the treatment groups.
However, patients with BRCA1 or BRCA2 mutations experience significantly greater objective response and PFS with carboplatin than docetaxel (objective response P = 0.03), Dr. Tutt noted. The median PFS for patients with BRCA1/2 mutations in the carboplatin group was 6.8 months versus 3.1 months for BRCA1/2 mutation-negative patients in the carboplatin group, and 4.8 and 4.6 months, respectively, among patients with and without BRCA1/2 mutations in the docetaxel group, he reported.
Patients with non Basal-like (PAM50) tumors experienced a significantly better objective response rate in the docetaxel group than the carboplatin group (P < 0.01), he noted.
Toxicities were “as anticipated,” with febrile neutropenia and neuropathy more frequent in the docetaxel group than with carboplatin (Ps < 0.01).
- Tutt A, Ellis P, Kilburn L et al. S3-01. Presented at: San Antonio Breast Cancer Symposium 2014. Dec. 9-13, 2014; San Antonio, TX.