PARPing back.

The BrighTNess trial showed that carboplatin and not veliparib (a PARP inhibitor) doubled pathologic complete response (pCR) rate for triple negative breast cancer, defying the hypothesis it would respond well to both agents. So let’s take a step back. In the phase 3 EMBRACA trial, patients with refractory or metastatic breast cancer and a germline BRCA mutation were randomized to physician’s choice chemo or the PARP inhibitor talazoparib plus one of four pre-specified systemic agents: capecitabine, gemcitabine, eribulin, or vinorelbine. Talazoparib plus chemo doubled the response rate from 27→ 62% and improved median progression free survival from 6→ 9 months at the cost of more hematologic toxicity. But the big caveat is that this trial didn’t include a platinum agent. So, while PARP inhibition is definitely active in this population, we’ll probably be seeing it next in combination, sequence, or compared to a platinum. TBL: Talazoparib plus non-platinum chemo is effective in patients with advanced BRCA-mutated breast cancer. | Litton, N Engl J Med 2018