Platinum Chemos: Cisplatin and Carboplatin

CONCLUSIONS AND FUTURE DIRECTIONS

There is growing evidence to suggest that platinum-based therapy may have a role to play in both advanced and early-stage TNBC, though results are not definitive. Three randomized phase II neoadjuvant trials have been reported, two of which demonstrated an improvement in pCR rates when carboplatin is added to anthracycline- and taxane-based chemotherapy, though this pCR improvement came at the cost of an increase in toxicity. Definitive results from phase III trials demonstrating improvement in long-term outcomes such as event-free and overall survival are not yet available, and it remains unclear how to optimally incorporate platinums into neoadjuvant therapy, as toxicity is enhanced when platinum is incorporated as an add-on to standard combination chemotherapy backbones. A randomized phase III trial of carboplatin versus docetaxel as first-line treatment for metastatic TNBC is nearing completion and will offer important evidence in the advanced disease setting.

In both early and advanced disease settings, response rates appear to be influenced by germline BRCA1 and BRCA2 mutation status, and BRCA1 andBRCA2 mutation status has emerged as an important potential biomarker for platinum therapy. Outside of the BRCA mutant setting, there is certainly good reason to believe that there are patients with sporadic TNBC who stand to benefit greatly from a platinum-based approach. Tumor-based assays that detect levels of genomic scarring caused by the accumulation of DNA damage over time secondary to underlying DNA repair defects, such as the Myriad HRD assay, have potential to identify non-BRCA1 or BRCA2 mutation carriers with “BRCA-like” breast cancer, who may respond to DNA repair-targeted treatment strategies, such as platinum agents. In addition to this LOH-based measure of genomic instability, other promising assays are in development, including the telomeric allelic imbalance (TAI) and large-scale state transitions (LST) assays.26,27 Prospective evaluation of these biomarkers in clinical trials is important to determine the ultimate effect that these assays may have for selecting patients with TNBC for platinum therapy. Careful randomized clinical trial designs that incorporate biomarkers of response hold the key to determining the clinical potential of platinum-based therapy in TNBC.

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