title: Evaluation of rucaparib and companion diagnostics in the PARP inhibitor landscape for recurrent ovarian cancer therapy.
abstract: Rucaparib camsylate (CO-338; 8-fluoro-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indol-6-one ((1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl)methanesulfonic acid salt) is a PARP1, 2 and 3 inhibitor. Phase I studies identified a recommended Phase II dose of 600 mg orally twice daily. ARIEL2 Part 1 established a tumor genomic profiling test for homologous recombination loss of heterozygosity quantification using a next-generation sequencing companion diagnostic (CDx). Rucaparib received US FDA Breakthrough Therapy designation for treatment of platinum-sensitive BRCA-mutated advanced ovarian cancer patients who received greater than two lines of platinum-based therapy. Comparable to rucaparib development, other PARP inhibitors, such as olaparib, niraparib, veliparib and talazoparib, are developing CDx tests for targeted therapy. PARP inhibitor clinical trials and CDx assays are discussed in this review, as are potential PARP inhibitor combination therapies and likely resistance mechanisms.
authors.affiliation: Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.|McGovern Medical School, formerly The University of Texas Health Science Center at Houston (UTHealth) Medical School, Houston, TX, USA.
authors.forename: Zachary B
authors.initials: ZB
authors.lastname: Jenner
authors.affiliation: Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.affiliation: Department of Gynecologic Oncology & Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Coleman
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000627:therapeutic use*; D016879:Salvage Therapy / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C531549:rucaparib
keywords: CO-338; PARP inhibitor; companion diagnostic; ovarian cancer; rucaparib