Antitumor activity and safety of the PARP inhibitor rucaparib in patients with high-grade ovarian carcinoma and a germline or somatic BRCA1 or BRCA2 mutation: Integrated analysis of data from Study 10 and ARIEL2

Oza, Amit M.; Tinker, Anna V.; Oaknin, Ana; Shapira‐Frommer, Ronnie; McNeish, Iain A.; Swisher, Elizabeth M.; Ray‐Coquard, Isabelle; Bell‐McGuinn, Katherine M.; Coleman, Robert L.; O’Malley, David M.; Leary, Alexandra; Chen, Lee May; Provencher, Diane; Ma, Ling; Brenton, James D.; Konecny, Gottfried E.; Castro, Cesar M.; Giordano, Heidi; Maloney, Lara; Goble, Sandra; Lin, Kevin K.; Sun, James; Raponi, Mitch; Rolfe, Lindsey; Kristeleit, Rebecca

doi:10.1016/j.ygyno.2017.08.022

Cited by 230 publications

(209 citation statements)

References 26 publications

(33 reference statements)

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“…Two studies282 283 have clearly shown a benefit for monotherapy with a PARP inhibitor in BRCA -mutated, relapsed high-grade ovarian carcinoma. A combination of two studies with rucaparib, ARIEL2 and study 10, led to the EMA approval of rucaparib in Europe as a monotherapy for relapsed or progressive BRCA -mutated (germline and/or somatic) HGSC, previously treated with ≥2 lines of platinum-based chemotherapy and unsuitable for further treatment with platinum-based chemotherapy 283. In Europe, the license for monotherapy is restricted to rucaparib and is only indicated for in patients with ‘platinum-sensitive’ disease 284.…”

Section: Resultsmentioning

confidence: 99%

ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease

Colombo

Sessa

Bois

et al. 2019

Int J Gynecol Cancer

312

425

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The development of guidelines is one of the core activities of the European Society for Medical Oncology (ESMO) and European Society of Gynaecologial Oncology (ESGO), as part of the mission of both societies to improve the quality of care for patients with cancer across Europe. ESMO and ESGO jointly developed clinically relevant and evidence-based recommendations in several selected areas in order to improve the quality of care for women with ovarian cancer. The ESMO–ESGO consensus conference on ovarian cancer was held on April 12–14, 2018 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of ovarian cancer. Before the conference, the expert panel worked on five clinically relevant questions regarding ovarian cancer relating to each of the following four areas: pathology and molecular biology, early-stage and borderline tumours, advanced stage disease and recurrent disease. Relevant scientific literature, as identified using a systematic search, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. The recommendations presented here are thus based on the best available evidence and expert agreement. This article presents the recommendations of this ESMO–ESGO consensus conference, together with a summary of evidence supporting each recommendation.

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Section: Resultsmentioning

confidence: 99%

ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease

Colombo

Sessa

Bois

et al. 2019

Int J Gynecol Cancer

312

425

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“…31 Rucaparib, another PARP inhibitor, has also been approved for treatment of patients with advanced ovarian cancer with germline or somatic BRCA1/2 mutations, on the basis of the combined analysis of the Study 10 and ARIEL2 phase II trials that showed an objective response rate of 54% and a median duration of response of 9.2 months with monotherapy. 32,33 In addition, in patients with recurrent ovarian cancer treated with maintenance niraparib, prolonged PFS was seen not only in the germline BRCA1/2 mutation cohort (21.0 months v 5.5 months) but also in the nongermline BRCA1/2 mutation cohort with high MyChoice HRD scores (12.9 months v 3.8 months), 34 leading to FDA approval of niraparib as maintenance treatment.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of Homologous Recombination–Related Gene Mutations Across Multiple Cancer Types

Heeke

Pishvaian

Lynce

et al. 2018

JCO Precision Oncology

247

204

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Purpose The prevalence of homologous recombination DNA damage repair (HR-DDR) deficiencies among all tumor lineages is not well characterized. Therapy directed toward homologous recombination DDR deficiency (HRD) is now approved in ovarian and breast cancer, and there may be additional opportunities for benefit for patients with other cancers. Comprehensive evaluations for HRD are limited in part by the lack of a uniform, cost-effective method for testing and defining HRD. Methods Molecular profiles of 52,426 tumors were reviewed to identify pathogenic mutations in the HR-DDR genes ARID1A, ATM, ATRX, BAP1, BARD1, BLM, BRCA1/2, BRIP1, CHEK1/2, FANCA/C/D2/E/F/G/L, MRE11A, NBN, PALB2, RAD50, RAD51, RAD51B, or WRN. From solid tumors submitted to Caris Life Sciences, molecular profiles were generated using next-generation sequencing (NGS; average read depth, 500×). A total of 17,566 tumors were sequenced with NGS600 (n = 592 genes), and 34,860 tumors underwent hotspot Illumina MiSeq platform testing (n = 47 genes). Results Of the tumors that underwent NGS600 testing, the overall frequency of HRDDR mutations detected was 17.4%, and the most commonly mutated lineages were endometrial (34.4%; n = 1,475), biliary tract (28.9%; n = 343), bladder (23.9%; n = 201), hepatocellular (20.9%; n = 115), gastroesophageal (20.8%; n = 619), and ovarian (20.0%; n = 2,489). Least commonly mutated lineages included GI stromal (3.7%; n = 108), head and neck (6.8%; n = 206), and sarcoma (9.3%; n = 592). ARID1A was the most commonly mutated gene (7.2%), followed by BRCA2 (3.0%), BRCA1 (2.8%), ATM (1.3%), ATRX (1.3%), and CHEK2 (1.3%). Conclusions HR-DDR mutations were seen in 17.4% of tumors across 21 cancer lineages, providing a path to explore the role of HRD-directed therapies, including poly-ADP ribose polymerase inhibitors, DNA-damaging chemotherapies, and newer agents such as ATR inhibitors.

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“…Rucaparib (Clovis Oncology, Boulder, CO) is an oral poly(ADP‐ribose) polymerase (PARP) inhibitor approved by the US Food and Drug Administration (FDA) as monotherapy for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum‐based chemotherapy and for treatment of adult patients with deleterious BRCA1 or BRCA2 mutation (germline and/or somatic)‐associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies …”

mentioning

confidence: 99%

Evaluation of Drug–Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P‐gp Substrates in Patients With an Advanced Solid Tumor

Xiao

Nowak²,

Tomaszewska-Kiecana

et al. 2018

Clinical Translational Sci

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This phase I study (CO‐338‐044; NCT02740712), conducted in patients with advanced solid tumors, evaluated the effect of the poly(ADP‐ribose) polymerase (PARP) inhibitor rucaparib on the pharmacokinetics (PK) of caffeine 200 mg, warfarin 10 mg, omeprazole 40 mg, and midazolam 2 mg (cytochrome P450 (CYP) 1A2, CYP2C9, CYP2C19, and CYP3A substrates; dosed as a cocktail) and digoxin 0.25 mg (P‐glycoprotein (P‐gp) substrate; dosed separately) without rucaparib and following oral rucaparib 600 mg b.i.d. Geometric mean (GM) ratios (90% confidence interval (CI)) of area under the concentration‐time curve (AUC) from time zero to last quantifiable measurement with and without rucaparib were: caffeine, 2.26 (1.93–2.65); S‐warfarin, 1.49 (1.40–1.58); omeprazole, 1.55 (1.32–1.83); midazolam, 1.39 (1.14–1.68); and digoxin, 1.20 (1.12–1.29). There was limited effect on peak concentration of the substrates (GM ratios, 0.99–1.13). At steady state, rucaparib 600 mg b.i.d. moderately inhibited CYP1A2, weakly inhibited CYP2C9, CYP2C19, and CYP3A, and marginally increased digoxin exposure.

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Antitumor activity and safety of the PARP inhibitor rucaparib in patients with high-grade ovarian carcinoma and a germline or somatic BRCA1 or BRCA2 mutation: Integrated analysis of data from Study 10 and ARIEL2

Abstract: Rucaparib has antitumor activity in advanced BRCA1/2-mutated HGOC and a manageable safety profile.

Cited by 230 publications

References 26 publications

ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease

ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease

Prevalence of Homologous Recombination–Related Gene Mutations Across Multiple Cancer Types

Evaluation of Drug–Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P‐gp Substrates in Patients With an Advanced Solid Tumor

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