Phase II Study of Maintenance Rucaparib in Patients With Platinum-Sensitive Advanced Pancreatic Cancer and a Pathogenic Germline or Somatic Variant in <i>BRCA1</i>, <i>BRCA2</i>, or <i>PALB2</i>.

Abstract

Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), is approved as maintenance therapy for patients with advanced pancreatic cancer (PC) and a germline <i>BRCA1</i> or <i>BRCA2</i> pathogenic variant (PV). This investigator-initiated, single-arm phase II study assessed the role of the PARPi rucaparib as maintenance therapy in advanced PC with germline or somatic PV in <i>BRCA1</i>, <i>BRCA2</i>, or <i>PALB2</i>. Eligible patients had advanced PC; germline (g) or somatic (s) PVs in <i>BRCA1</i>, <i>BRCA2</i>, or <i>PALB2</i>, and received at least 16 weeks of platinum-based chemotherapy without evidence of platinum resistance. Chemotherapy was discontinued and patients received rucaparib 600 mg orally twice a day until progression. The primary end point was the progression-free survival (PFS) rate at 6 months (PFS6). Secondary end points included safety, ORR, disease control rate, duration of response, and overall survival. Of 46 enrolled patients, 42 were evaluable (27 g<i>BRCA2</i>, seven g<i>BRCA1</i>, six g<i>PALB2</i>, and two s<i>BRCA2</i>). PFS6 was 59.5% (95% CI, 44.6 to 74.4), median PFS was 13.1 months (95% CI, 4.4 to 21.8), and median overall survival was 23.5 months (95% CI, 20 to 27). The PFS at 12 months was 54.8%. ORR of the 36 patients with measurable disease was 41.7% (3 complete responses; 12 partial responses; 95% CI, 25.5 to 59.2), and disease control rate was 66.7% (95% CI, 49.0 to 81.4). Median duration of response was 17.3 months (95% CI, 8.8 to 25.8). Responses occurred in patients with <i>gBRCA2</i> (41%, 11 out of 27), <i>gPALB2</i> (50%, 3 out of 6), and <i>sBRCA2</i> (50%, 1 out of 2). No new safety signals were noted. Maintenance rucaparib is a safe and effective therapy for platinum-sensitive, advanced PC with a PV in <i>BRCA1</i>, <i>BRCA2</i>, or <i>PALB2</i>. The finding of efficacy in patients with g<i>PALB2</i> and s<i>BRCA2</i> PVs expands the population likely to benefit from PARPi beyond g<i>BRCA1</i>/<i>2</i> PV carriers.