Rucaparib (Rubraca™) is an oral, small molecule, poly (ADP-ribose) polymerase inhibitor being developed by Clovis Oncology, Inc. (Boulder, CO, USA) for the treatment of solid tumours. It has been approved in the USA as monotherapy for the treatment of patients with deleterious BRCA mutation (germline and/or somatic) associated advanced ovarian cancer who have been treated with two or more chemotherapies. A marketing authorization application for rucaparib for the same indication has been submitted to the European Medicines Agency. Rucaparib is also under phase II or III investigation in ovarian, breast and prostate cancer. This article summarizes the milestones in the development of rucaparib leading to this first approval for ovarian cancer.
KeywordsOvarian Cancer Objective Response Rate Advanced Ovarian Cancer Royalty Payment Homologous Recombination Deficiency
The preparation of this review was not supported by any external funding. During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. Y.Y. Syed is a salaried employee of Adis, Springer SBM.
- 1.Clovis Oncology Inc. Prescribing information for RubracaTM (rucaparib) tablets, for oral use. 2016. http://www.fda.gov. Accessed 9 Jan 2017.
- 5.Clovis Oncology Inc. Clovis Oncology, Inc. receives license for worldwide development and commercialization rights to Pfizer’s oral and IV PARP inhibitor PF-01367338 [media release]. 2011. http://www.clovisoncology.com.
- 6.Clovis Oncology. SEC filings: 10K annual report for 2013. 2013. http://www.clovisoncology.com. Accessed 21 Feb 2017.
- 7.Lonza. Lonza and Clovis Oncology sign strategic long-term manufacturing agreement to secure supply of rucaparib [media release]. 2016. http://www.lonza.com.
- 9.Kern KA, Zhang S, Shalinsky DR, et al. Comparative PARP enzyme inhibition of PF-01367338, olaparib, and MK-4827 [abstract no. e13552]. J Clin Oncol. 2011;29(Suppl 15). doi: 10.1200/jco.2011.29.15_suppl.e13552
- 12.Drew Y, Ledermann J, Hall G, et al. Phase 2 multicentre trial investigating intermittent and continuous dosing schedules of the poly(ADP-ribose) polymerase inhibitor rucaparib in germline BRCA mutation carriers with advanced ovarian and breast cancer. Br J Cancer. 2016;114(12):723–30.CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Ihnen M, Zu Eulenburg C, Kolarova T, et al. Therapeutic potential of the poly(ADP-ribose) polymerase inhibitor rucaparib for the treatment of sporadic human ovarian cancer. Mol Cancer Ther. 2013;12(6):1002–15.Google Scholar
- 18.Audrey LC, Vanessa C, Marie K. The PARP inhibitor, Rucaparib enhance the sensitivity to Trabectedin in soft tissue sarcomas cell lines and in patient xenograft model [abstract no. 3002]. Cancer Res. 2016;76(Suppl 14). doi: 10.1158/1538-7445.AM2016-3002
- 22.Kotsopoulos IC, Begbie JA, Mukhopadhyay A, et al. In vitro single agent rucaparib cytotoxicity and cisplatin chemo-potentiation in cervical cancer cell lines [abstract no. IGCS-0702]. Int J Gynecol Cancer. 2016;26(Suppl 3):374.Google Scholar
- 26.Cullinane C, Waldeck K, Eu P, et al. The PARP inhibitor, rucaparib enhances the antitumor activity of 177Lu-DOTA-octreotate radionuclide therapy in preclinical models of neuroendocrine tumor [abstract no. 1800]. Cancer Res. 2015;75(Suppl 15). doi: 10.1158/1538-7445.AM2015-1800
- 28.Ali M, Kamjoo M, Thomas HD, et al. The clinically active PARP inhibitor AG014699 ameliorates cardiotoxicity but does not enhance the efficacy of doxorubicin, despite improving tumor perfusion and radiation response in mice. Mol Cancer Ther. 2011;10(12):2320–9.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.McCormick A, Nakjang S, Donoghue P, et al. The role of homologous recombination recovery in cisplatin and rucaparib resistance in ovarian cancer [abstract no. ESGO-0857]. Int J Gynecol Cancer. 2015;25(Suppl 9):627.Google Scholar
- 35.Kristeleit RS, Shapira-Frommer R, Oaknin A, et al. Clinical activity of the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib in patients (pts) with high-grade ovarian carcinoma (HGOC) and a BRCA mutation (BRCAmut): analysis of pooled data from study 10 (parts 1, 2a, and 3) and ARIEL2 (parts 1 and 2) [abstract no. 856O]. In: European Society for Medical Oncology 2016 Congress. 2016.Google Scholar
- 37.Coleman RL, Swisher EM, Oza AM, et al. Refinement of prespecified cutoff for genomic loss of heterozygosity (LOH) in ARIEL2 part 1: a phase II study of rucaparib in patients (pts) with high grade ovarian carcinoma (HGOC) [abstract no. 5540 plus poster]. J Clin Oncol. 2016;34(Suppl).Google Scholar
- 38.Kristeleit RS, Burris HA, LoRusso P, et al. Phase 1/2 study of oral rucaparib: final phase 1 results [abstract no. 2573]. J Clin Oncol. 2014;32(Suppl 5).Google Scholar
- 39.Miller K, Tong Y, Jones DR, et al. Cisplatin with or without rucaparib after preoperative chemotherapy in patients with triple negative breast cancer: final efficacy results of Hoosier Oncology Group BRE09-146 [abstract no. 1082]. J Clin Oncol. 2015;33(Suppl 15).Google Scholar
- 40.Domchek SM, Hendifar AE, McWilliams RR, et al. RUCAPANC: an open-label, phase 2 trial of the PARP inhibitor rucaparib in patients (pts) with pancreatic cancer (PC) and a known deleterious germline or somatic BRCA mutation [abstract no. 4110 plus poster]. J Clin Oncol. 2016;34(Suppl).Google Scholar
- 41.Foundation Medicine Inc. FoundationFocus™ CDxBRCA: draft summary of technical information. 2017. http://www.fda.gov. Accessed 20 Feb 2017.
- 42.Clovis Oncology. Clovis Oncology announces Q2 2016 operating results and corporate update [media release]. 8 Aug 2016. http://www.clovisoncology.com.
- 43.Toms C, Chopra N, Houlton L, et al. Window study of the PARP inhibitor rucaparib in patients with primary triple negative or BRCA1/2 related breast cancer (RIO) [abstract no. 219TiP]. Ann Oncol. 2016;27(Suppl 6).Google Scholar