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Clinical Trial
. 2021 Aug 1;39(22):2497-2505.
doi: 10.1200/JCO.21.00003. Epub 2021 May 10.

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

Kim A Reiss  1   2 , Rosemarie Mick  1   3 , Mark H O'Hara  1   2 , Ursina Teitelbaum  1   2 , Thomas B Karasic  1   2 , Charles Schneider  1   2 , Stacy Cowden  1 , Traci Southwell  1 , Janae Romeo  1 , Natallia Izgur  1 , Zain M Hannan  1 , Rashmi Tondon  1   4 , Katherine Nathanson  1   2 , Robert H Vonderheide  1   2 , Max M Wattenberg  1   2 , Gregory Beatty  1   2 , Susan M Domchek  1   2
Affiliations
Clinical Trial

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

Kim A Reiss et al. J Clin Oncol. .

Abstract

Purpose: Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), is approved as maintenance therapy for patients with advanced pancreatic cancer (PC) and a germline BRCA1 or BRCA2 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 BRCA1, BRCA2, or PALB2.

Patients and methods: Eligible patients had advanced PC; germline (g) or somatic (s) PVs in BRCA1, BRCA2, or PALB2, 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.

Results: Of 46 enrolled patients, 42 were evaluable (27 gBRCA2, seven gBRCA1, six gPALB2, and two sBRCA2). 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 gBRCA2 (41%, 11 out of 27), gPALB2 (50%, 3 out of 6), and sBRCA2 (50%, 1 out of 2). No new safety signals were noted.

Conclusion: Maintenance rucaparib is a safe and effective therapy for platinum-sensitive, advanced PC with a PV in BRCA1, BRCA2, or PALB2. The finding of efficacy in patients with gPALB2 and sBRCA2 PVs expands the population likely to benefit from PARPi beyond gBRCA1/2 PV carriers.

Trial registration: ClinicalTrials.gov NCT03140670.

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Conflict of interest statement

Kim A. ReissHonoraria: MJH Life SciencesResearch Funding: Lilly, Clovis Oncology, Bristol Myers Squibb, Tesaro, GlaxoSmithKline, Parker Institute for Cancer Immunotherapy Rosemarie MickStock and Other Ownership Interests: Editas Medicine Mark H. O'HaraConsulting or Advisory Role: Natera, GeneosResearch Funding: Bristol Myers Squibb, Celldex, Parker Institute for Cancer Immunotherapy, Lilly, Arcus Biosciences, NateraTravel, Accommodations, Expenses: AstraZeneca/MedImmune Thomas B. KarasicHonoraria: Exelixis, Incyte, PfizerResearch Funding: Syndax, Taiho Pharmaceutical, Celgene, H3 Biomedicine, Bristol Myers Squibb, Lilly, Sirtex Medical, Tempest Therapeutics Robert H. VonderheidePatents, Royalties, Other Intellectual Property: Receives royalties from Boston Children's Hospital for a licensed research-only monoclonal antibody and inventor on a licensed patent regarding cancer vaccine antigens Max M. WattenbergConsulting or Advisory Role: NanOlogyResearch Funding: HiberCell, Lilly Gregory BeattyStock and Other Ownership Interests: Johnson & JohnsonHonoraria: Janssen, IncyteConsulting or Advisory Role: Incyte, Bristol Myers Squibb, Array BioPharma, Vaccinex, Seattle Genetics, Opsona Therapeutics, AstraZeneca, Aduro Biotech, Merck, BiolineRx, Genmab, Janssen, Shattuck Labs, Boehringer Ingelheim, Cour Pharmaceuticals, Monopteros Therapeutics, NanoGhost, Pancreatic Cancer Action Network, Seagen, Molecular PartnersResearch Funding: Novartis, Incyte, Biothera, Halozyme, Bristol Myers Squibb, Verastem, Janssen, Newlink Genetics, Arcus Biosciences, HiberCell, Monopteros TherapeuticsPatents, Royalties, Other Intellectual Property: Inventor of intellectual property related to mesothelin CAR T cells that is licensed by the University of Pennsylvania to Novartis and inventor of intellectual property related to mesothelin CAR T cells that is licensed by the University of Pennsylvania to TMUNITY Susan M. DomchekHonoraria: AstraZeneca, Clovis Oncology, Bristol Myers SquibbResearch Funding: AstraZeneca, Clovis OncologyOpen Payments Link: https://openpaymentsdata.cms.gov/physician/917904No other potential conflicts of interest were reported.

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