PARP/Checkpoint Inhibition in TNBC: The TOPACIO Trial

Transcript: Joyce A. O’Shaughnessy, MD: We’ve had an update on the TOPACIO trial in women with metastatic triple-negative breast cancer [TNBC], and the TOPACIO trial combined the PARP inhibitor niraparib with the checkpoint inhibitor pembrolizumab. And this was a mixed population of women with germline BRCA mutations or wild-type BRCA in triple-negative breast cancer. And the overall response rate in this trial was 28%. It was largely a pretreated population. In the germline BRCA population, the response rate was 60%, and that’s what we had seen with talazoparib and with olaparib in the big phase III trials with just single-agent PARP inhibitors. So the addition of the checkpoint inhibitor did not increase the response rate. However, the durability of the responses was much more impressive to my eye than with a PARP inhibitor alone. And we’re getting longer-duration follow-up now on the TOPACIO trial.

So what was interesting is this new analysis started looking for biomarkers of benefit for the PARP inhibitor and the checkpoint inhibitor, and of course, BRCA mutation status was clearly one, and some of those responses were getting to be quite durable. But in the BRCA wild-type patients, it was found that other mutations in homologous recombination deficiency in the tumor may be predictive of benefit, because some of these patients had responses, and durable responses. So, for example, CHEK2 somatic mutations or ATM mutations were also found and a couple of other mutations in other homologous recombination genes where we know the germline mutations in those genes led to a BRCA-like state and a much higher risk for developing breast cancer and other cancers.

So these are very interesting data combining a PARP inhibitor and checkpoint inhibitor in women whose cancers have other mutations, besides BRCA, showing response rates and some durable responses. It’s really very early. It’s quite exploratory. But it gives us hope that this strategy may be able to be expanded beyond just the germline BRCA population.

Transcript Edited for Clarity