Efficacy
The objective response rate (ORR) in the intention to treat population (ITT) was 31.4% in the carboplatin group vs 34% in the docetaxel group (95% CI -12.1 to 6.9; p=0.66). The difference between median progression-free survival (mPFS) and median overall survival (mOS) did not reach statistical significance between groups in the ITT population.r
Outcomes |
Time to event or response rate |
p-value |
|
Carboplatin |
Docetaxel |
|
mPFS |
3.1 months |
4.4 months |
0.40 |
mOS |
12.8 months |
12 months |
0.96 |
© Nature Medicine 2018
Subgroup analysis of BRCA1/2 germline mutation subgroups showed patients who were mutation positive (25 carboplatin and 18 docetaxel subjects) had an improved ORR with carboplatin compared with docetaxel (68% vs 33.3% p=0.03; remained statistically significant after adjustment for known prognostic factors p=0.01). mPFS also favoured carboplatin use in the mutation positive population (6.8 vs 4.4 months, p=0.002). There was no statistically significant difference in the mutation negative subgroup in terms of ORR or mPFS. mOS did not reach statistical significance in either group. Of the patients with germline BRCA1 or BRCA2 mutations, 4 and 7 had ER positive disease respectively.
Differences in the tumour BRCA, BRCA methylation, mRNA-low and homologous recombination deficiency did not reach statistical significance. In the non-basal like subgroup (18 patients in both the carboplatin and docetaxel groups respectively), ORR favoured docetaxel (ORR 16.7% vs 72.2%, p=0.002).
The main limitations of the study include a limit in the number of cycles of chemotherapy given, crossover of treatments, and small numbers of BRCA mutation patients.
Progression-free survival (overall and BRCA subgroup)r
© Nature Medicine 2018
These findings are supported by a multicentre phase II study (TBCRC009) by Isakoff et al, of platinum monotherapy in patients with metastatic triple negative breast cancer.r Patients were treated with single agent carboplatin (n= 43) or cisplatin (n= 43) in the first or second line setting. In patients with a germline BRCA 1/2 mutation (n=11), there was an increased ORR observed (54.5%) versus BRCA wild type (19.7%) (p=0.022). 7 of these patients received cisplatin, and 4 received carboplatin.