Study: In Small Sample of Patients With Advanced Pancreatic Cancer With Progressive Disease on PARP Inhibitor, Chemotherapy Retains Some Activity

In a small study of individuals with advanced pancreatic cancer with progressive disease on PARP inhibitors, chemotherapy retained some of its activity, according to a session at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

Investigators said that further studies are underway in order to identify predictors of response and/or resistance to post-PARP inhibitor treatment.

The investigators enrolled a total of 42 individuals in the study, 31 of whom experienced disease progression. Patients with advanced pancreatic cancer and germline or somatic BRCA1, BRCA2, or PALB2 mutation treated with at least 16 weeks of platinum-based chemotherapy without progression were enrolled, with the investigators treating them with rucaparib until progression or unacceptable toxicity.

Additionally, at the time of progression, individuals were treated with the physician’s choice of chemotherapy; investigators evaluated the objective response rate by RECIST 1.1. The overall survival (OS) and time to second progression (PFS2) calculated from trial enrollment and progression free survival (PFS) on chemotherapy by regimen were the secondary endpoints. Additionally, time-to-event was analyzed by the Kaplan-Meier method and censored at date of their last clinic visit. The cutoff date was December 10, 2021.

Investigators defined OS as the time the patient was enrolled until death. PFS2 was defined as time from study enrollment until the second progression, while PFS was defined as time from chemotherapy initiation after rucaparib and progression.

Of the individuals with disease progression, 22 received second-line chemotherapy with 9 who were treated with an oxaliplatin-based regimen, 9 with a cisplatin-based regimen, and 4 were treated with non-platinum regimens.

Investigators balanced the demographics between those who were treated with platinum and non-platinum chemotherapy. All individuals who received second-line chemotherapy regimens met the PFS2 endpoint; all but 1 individual had died at the point of the data cutoff.

Furthermore, no individuals had a complete response and only 5 had a partial response. One of the 9 individuals with cisplatin had a partial response, 3 of 9 treated with oxaliplatin had a partial response, and 1 of 4 who were treated with non-platinum had a partial response.

The overall response for non-platinum treatments was 20.3 months, cisplatin was 13.8 months, and oxaliplatin was 19 months. The PFS2 was 6.6 months, 9.1 months, 9.4 months, respectively. PFS was 3.9 months, 2.9 months, 2.7 months, respectively. The ORR was 25%, 11.1%, and 33.3%, respectively.

The study findings assessed by the investigators were from a single arm, phase 2 study investigating maintenance rucaparib in individuals with platinum-sensitive advanced pancreatic cancer and a pathogenic variant in BRCA1, BRCA2, or PALB2. The optimal treatment following progression on PARP inhibitors was not determined in the study.

Reference

Brown T. A descriptive study on the treatment and outcomes of patients with platinum-sensitive, advanced, BRCA- or PALB2-related pancreatic cancer who have progressed on rucaparib. American Society of Clinical Oncology. June 02, 2022; 4131-4131. doi: 10.1200/JCO.2022.40.16_suppl.4131