Kim A. Reiss Binder, MD, Reviews PARP Plus Immunotherapy in Platinum-Sensitive Advanced Pancreatic Adenocarcinoma

At the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, CancerNetwork^® spoke with Kim A. Reiss Binder, MD, assistant program director of the Hematology/Oncology Fellowship Program at Penn Medicine, and assistant professor of medicine at the Hospital of the University of Pennsylvania. She discussed her poster presentation of which was a randomizedphase 1b/2 Parpvax trial (NCT03404960) for of patients with platinum-sensitive advanced pancreatic cancer adenocarcinoma being treated with niraparib (Zejula) plus either , nivolumab (Opdivo) or , and ipilimumab (Yervoy) compared with niraparib plus nivolumab.

Transcript:

This was a study of patients with advanced disease pancreatic cancer, who had at least stable disease for 4 months or more on platinum-based chemotherapy. We then discontinued chemotherapy and randomized patients to get either a PARP inhibitor of niraparib plus nivolumab or niraparib and plus ipilimumab. The top line finding was the PFS [progression-free survival], which was our primary endpoint. The arms were also not meant to be compared, they are parallel arms both looking at separate primary endpoints which was PFS in both cases.

We aimed for a PFS-6 [PFS rate at 6 months] of 44%, and the results show that PARP inhibitor plus nivolumab reached a PFS-6 of only 20% with a median PFS of 1.8 months. The PARP [inhibitor] plus [ipilimumab] reached a PFS-6 of 59.6% and a median PFS of 8.1%. The take home is that PARP [inhibitors] plus anti–-CTLA-4 was successful in delaying progression in patients with advanced pancreatic cancer and platinum-sensitive disease, while PARP [inhibitors] and PD-L1, PARP [inhibitors] andlike nivolumab, did not do that. Secondly, and maybe even more importantly, when we eliminated in a secondary analysis all the patients with DDR [DNA damage responserepair] variants including—BRCA and PALB2, but also noncanonical DDR variants—,in a secondary analysis, the results held. In other words, the patients without a clinically identified DDR deficiency benefited from the therapy as well.

Reference

Reiss KA, Mick R, Teitelbaum UR, et al. A randomized phase Ib/II study of niraparib (nira) plus nivolumab (nivo) or ipilimumab (ipi) in patients (pts) with platinum-sensitive advanced pancreatic cancer (aPDAC). J Clin Oncol. 2022;40(suppl 16):4021. doi: 10.1200/JCO.2022.40.16_suppl.4021