PARP Inhibitor Maintenance Therapy for Pancreatic Cancer With BRCA Mutation

At the 2019 Great Debates and Updates in GI Malignancies meeting, Eileen O'Reilly, MD, debated in favor of using PARP inhibitors as maintenance therapy for patients with BRCA mutation–positive pancreatic cancer.

Transcript:

Eileen O'Reilly, MD: Good morning. This is Eileen O'Reilly from Memorial Sloan Kettering. Greetings from a beautiful sunny Chicago day here at the Great Debates in Chicago, I believe for the first time. Very, very exciting.

We had a nice debate this afternoon, Jordan Berlin and I, addressing the topic of maintenance therapy in pancreas cancer, and specifically in the BRCA setting.

The side I have to argue, and I believe the more potent side, is continuation or use of a PARP inhibitor as a maintenance therapy, and Dr. Berlin, addressing the side of continuation of cytotoxic therapy. The bottom line here is, we don't have comparative data comparing PARP inhibitors versus chemotherapy in this maintenance setting, in germline BRCA.

Having said that, we have a lot of data indicating that PARP inhibitors are active in pancreas cancer, particularly in the germline and somatic BRCA and PALB2 mutated state in both a maintenance setting from the POLO Study that was presented at the plenary session at ASCO this year, from maintenance data with rucaparib that comes from U Penn, and from several other data sites.

The reason I would strongly argue that we do use PARP inhibitors in a maintenance setting are, they're well tolerated, they're oral, they give patients flexibility away from the burden of chemotherapy, and infusions and, etc.

Bringing in PARP inhibitors, and I think this is a key point, before resistance to platinum therapy, emerges as critical. We know that we lose a potential line of therapy by delaying. That's very strong argument in my opinion.

The counter point from Dr. Berlin is that we didn't see a survival advantage against placebos. If we didn't see it against placebo, is it likely that chemotherapy could be better than a PARP inhibitor?

That's very speculative. I don't think we can say yes or no. The philosophy of doing something that's tolerable and oral, as opposed to nothing, is compelling in an enriched targeted population where we have established proof-of-principle.