PMID- 28882436 OWN - NLM STAT- MEDLINE DCOM- 20171108 LR - 20240210 IS - 1095-6859 (Electronic) IS - 0090-8258 (Linking) VI - 147 IP - 2 DP - 2017 Nov TI - 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. PG - 267-275 LID - S0090-8258(17)31260-X [pii] LID - 10.1016/j.ygyno.2017.08.022 [doi] AB - OBJECTIVE: An integrated analysis was undertaken to characterize the antitumor activity and safety profile of the oral poly(ADP-ribose) polymerase inhibitor rucaparib in patients with relapsed high-grade ovarian carcinoma (HGOC). METHODS: Eligible patients from Study 10 (NCT01482715) and ARIEL2 (NCT01891344) who received a starting dose of oral rucaparib 600mg twice daily (BID) with or without food were included in these analyses. The integrated efficacy population included patients with HGOC and a deleterious germline or somatic BRCA1 or BRCA2 (BRCA1/2) mutation who received at least two prior chemotherapies and were sensitive, resistant, or refractory to platinum-based chemotherapy. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR) and progression-free survival (PFS). The integrated safety population included patients with HGOC who received at least one dose of rucaparib 600mg BID, irrespective of BRCA1/2 mutation status and prior treatments. RESULTS: In the efficacy population (n=106), ORR was 53.8% (95% confidence interval [CI], 43.8-63.5); 8.5% and 45.3% of patients achieved complete and partial responses, respectively. Median DOR was 9.2months (95% CI, 6.6-11.6). In the safety population (n=377), the most frequent treatment-emergent adverse events (AEs) were nausea, asthenia/fatigue, vomiting, and anemia/hemoglobin decreased. The most common grade >/=3 treatment-emergent AE was anemia/hemoglobin decreased. Treatment-emergent AEs led to treatment interruption, dose reduction, and treatment discontinuation in 58.6%, 45.9%, and 9.8% of patients, respectively. No treatment-related deaths occurred. CONCLUSIONS: Rucaparib has antitumor activity in advanced BRCA1/2-mutated HGOC and a manageable safety profile. CI - Copyright (c) 2017 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Oza, Amit M AU - Oza AM AD - Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto M5G 2M9, Canada. Electronic address: amit.oza@uhn.ca. FAU - Tinker, Anna V AU - Tinker AV AD - Division of Medical Oncology, Vancouver Cancer Centre, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver V5N4E6, Canada. FAU - Oaknin, Ana AU - Oaknin A AD - Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, 119-129, 08035 Barcelona, Spain. FAU - Shapira-Frommer, Ronnie AU - Shapira-Frommer R AD - Sheba Medical Center, Emek HaEla St 1, 52621 Ramat Gan, Israel. FAU - McNeish, Iain A AU - McNeish IA AD - Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Glasgow G61 1QH, UK. FAU - Swisher, Elizabeth M AU - Swisher EM AD - Department of Obstetrics and Gynecology, University of Washington, 1959 NE Pacific St, Seattle, WA 98195, USA. FAU - Ray-Coquard, Isabelle AU - Ray-Coquard I AD - GINECO, Centre Leon Berard and University Claude Bernard, 28 rue Laennec, 69373 Lyon, France. FAU - Bell-McGuinn, Katherine AU - Bell-McGuinn K AD - Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA. FAU - Coleman, Robert L AU - Coleman RL AD - The University of Texas MD Anderson Cancer Center, 1155 Herman Pressler Dr., CPB6.3590, Houston, TX 77030, USA. FAU - O'Malley, David M AU - O'Malley DM AD - The Ohio State University, James Cancer Center, M210 Starling Loving, 320 W 10th Ave, Columbus, OH 43210, USA. FAU - Leary, Alexandra AU - Leary A AD - GINECO, Gynecological Unit, Department of Medicine, Gustave Roussy Cancer Center and INSERM U981, 114 Rue Edouard-Vaillant, 94805 Villejuif, France. FAU - Chen, Lee-May AU - Chen LM AD - Department of Obstetrics, Gynecology, and Reproductive Sciences, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 550 16th St., 7th Floor, San Francisco, CA 94143-1702, USA. FAU - Provencher, Diane AU - Provencher D AD - Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), Institut du cancer de Montreal, Department of Obstetrics and Gynecology, Universite de Montreal, 1560 rue Sherbrooke Est, Montreal H2L 4M1, Canada. FAU - Ma, Ling AU - Ma L AD - Rocky Mountain Cancer Centers, 11750 W 2nd Pl #150, Lakewood, CO 80228, USA. FAU - Brenton, James D AU - Brenton JD AD - Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK. FAU - Konecny, Gottfried E AU - Konecny GE AD - David Geffen School of Medicine, University of California Los Angeles, 2825 Santa Monica Blvd, Suite 200, Santa Monica, CA 90404, USA. FAU - Castro, Cesar M AU - Castro CM AD - Massachusetts General Hospital Cancer Center, Harvard Medical School, 185 Cambridge St, 5th floor, Boston, MA 02114, USA. FAU - Giordano, Heidi AU - Giordano H AD - Clovis Oncology, Inc., 5500 Flatiron Parkway, Boulder, CO 80301, USA. FAU - Maloney, Lara AU - Maloney L AD - Clovis Oncology, Inc., 5500 Flatiron Parkway, Boulder, CO 80301, USA. FAU - Goble, Sandra AU - Goble S AD - Clovis Oncology, Inc., 5500 Flatiron Parkway, Boulder, CO 80301, USA. FAU - Lin, Kevin K AU - Lin KK AD - Clovis Oncology, Inc., 5500 Flatiron Parkway, Boulder, CO 80301, USA. FAU - Sun, James AU - Sun J AD - Foundation Medicine, Inc., 150 Second St, Cambridge, MA 02141, USA. FAU - Raponi, Mitch AU - Raponi M AD - Clovis Oncology, Inc., 5500 Flatiron Parkway, Boulder, CO 80301, USA. FAU - Rolfe, Lindsey AU - Rolfe L AD - Clovis Oncology, Inc., 5500 Flatiron Parkway, Boulder, CO 80301, USA. FAU - Kristeleit, Rebecca S AU - Kristeleit RS AD - University College London Cancer Institute, 72 Huntley St, London WC1E 6BT, UK. LA - eng GR - 15973/CRUK_/Cancer Research UK/United Kingdom GR - G0501974/MRC_/Medical Research Council/United Kingdom GR - G0601891/MRC_/Medical Research Council/United Kingdom PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article DEP - 20170904 PL - United States TA - Gynecol Oncol JT - Gynecologic oncology JID - 0365304 RN - 0 (BRCA1 Protein) RN - 0 (BRCA1 protein, human) RN - 0 (BRCA2 Protein) RN - 0 (BRCA2 protein, human) RN - 0 (Indoles) RN - 0 (Poly(ADP-ribose) Polymerase Inhibitors) RN - 8237F3U7EH (rucaparib) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - BRCA1 Protein/genetics MH - BRCA2 Protein/genetics MH - Carcinoma, Ovarian Epithelial MH - Female MH - *Genes, BRCA1 MH - *Genes, BRCA2 MH - *Germ-Line Mutation MH - Humans MH - Indoles/adverse effects/*therapeutic use MH - Middle Aged MH - Neoplasm Grading MH - Neoplasms, Glandular and Epithelial/*drug therapy/*genetics/pathology MH - Ovarian Neoplasms/*drug therapy/*genetics/pathology MH - Poly(ADP-ribose) Polymerase Inhibitors/adverse effects/*therapeutic use OTO - NOTNLM OT - Ovarian carcinoma OT - PARP inhibitor OT - Rucaparib OT - Somatic, germline BRCA mutation EDAT- 2017/09/09 06:00 MHDA- 2017/11/09 06:00 CRDT- 2017/09/09 06:00 PHST- 2017/05/15 00:00 [received] PHST- 2017/08/15 00:00 [revised] PHST- 2017/08/20 00:00 [accepted] PHST- 2017/09/09 06:00 [pubmed] PHST- 2017/11/09 06:00 [medline] PHST- 2017/09/09 06:00 [entrez] AID - S0090-8258(17)31260-X [pii] AID - 10.1016/j.ygyno.2017.08.022 [doi] PST - ppublish SO - Gynecol Oncol. 2017 Nov;147(2):267-275. doi: 10.1016/j.ygyno.2017.08.022. Epub 2017 Sep 4.