Abstract CT234: A Phase II, single arm study of maintenance rucaparib in patients with platinum-sensitive advanced pancreatic cancer and a pathogenic germline or somatic mutation in BRCA1, BRCA2 or PALB2
Authors: Binder Kim A. Reiss , Mick Rosemarie , O'Hara Mark , Teitelbaum Ursina , Karasic Thomas , Schneider Charles , O'Dwyer Peter J. , Carpenter Erica , Pantel Austin , Makvandi Mehran , Mankoff David , Nathanson Katherine , Maxwell Kara , Cowden Stacy , Fuhrer Mary Jane , Romeo Janae , Beatty Gregory L. , Domchek Susan 
Published: August 2019

Abstract
Background: PARP inhibitors have activity in multiple BRCA-related malignancies and have recently demonstrated dramatic efficacy as a maintenance strategy for platinum-sensitive ovarian cancer. Between 5-8% of patients with pancreatic cancer (PC) have a pathogenic mutation in BRCA1, BRCA2 or PALB2. Therefore, we initiated a single arm phase II clinical trial of maintenance monotherapy rucaparib in patients with advanced PC and a pathogenic germline or somatic BRCA or PALB2 mutation, whose cancer had not progressed following at least four months of platinum-based chemotherapy (NCT 03140670).
Methods: Patients were enrolled and treated with rucaparib 600mg PO BID until disease progression or unacceptable toxicity. The primary endpoint is progression free survival (PFS). Patients have previously received &gt;4 months of platinum-based chemotherapy without evidence of disease progression. However, patients with a medical contraindication to receiving the full four months of platinum have been permitted to enroll at the discretion of the primary investigator. Responses were determined using RECIST v1.1.
Results: As of December 31st, 2018, we have enrolled 24 of the planned 42 patients, of which 19 are evaluable for PFS at the time of this interim analysis. For these patients, the mutational distribution includes: 13 germline BRCA2, 3 germline BRCA1, 2 germline PALB2, 1 somatic BRCA2. Patients were predominantly female (84.2%) with a median age of 61 years (range: 35-81). Patients had received a median of four months (range 0.5-32 months) of prior platinum therapy for advanced disease. All patients were evaluable for toxicity. Overall, treatment with rucaparib was well tolerated without dose limiting toxicities. The most common adverse events that were at least possibly related to treatment included nausea (grade 1, 41.6%; grade 2, 4.2%), dysgeusia (grade 1, 33.3%) and fatigue (grade 1, 25%). One patient required dose reduction for nausea. The median PFS was 9.1 months from the start of rucaparib therapy with an ORR of 36.8% (six PRs; one CR). Disease control rate (CR + PR + SD) was 89.5% for at least eight weeks. Two patients (10.5%) had progressive disease at first follow-up scan two months after beginning treatment. Eight patients have been on rucaparib for &gt;6 months and two patients remain on treatment for &gt;1 year (13 months and 15 months). The seven responding patients include those with germline BRCA2 mutations (4 patients), germline PALB2 mutations (2 patients) and somatic BRCA2 mutation (1 patient).
Conclusions: Based on these early data, maintenance rucaparib following induction with platinum-based chemotherapy shows encouraging disease control with minimal toxicity in patients with platinum-sensitive advanced PC and a pathogenic mutation in BRCA1, BRCA2 or PALB2.
Citation Format: Kim A. Reiss Binder, Rosemarie Mick, Mark O'Hara, Ursina Teitelbaum, Thomas Karasic, Charles Schneider, Peter J. O'Dwyer, Erica Carpenter, Austin Pantel, Mehran Makvandi, David Mankoff, Katherine Nathanson, Kara Maxwell, Stacy Cowden, Mary Jane Fuhrer, Janae Romeo, Gregory L. Beatty, Susan Domchek. A Phase II, single arm study of maintenance rucaparib in patients with platinum-sensitive advanced pancreatic cancer and a pathogenic germline or somatic mutation in BRCA1, BRCA2 or PALB2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT234.