Amit M Oza1, Anna V Tinker2, Ana Oaknin3, Ronnie Shapira-Frommer4, Iain A McNeish5, Elizabeth M Swisher6, Isabelle Ray-Coquard7, Katherine Bell-McGuinn8, Robert L Coleman9, David M O'Malley10, Alexandra Leary11, Lee-May Chen12, Diane Provencher13, Ling Ma14, James D Brenton15, Gottfried E Konecny16, Cesar M Castro17, Heidi Giordano18, Lara Maloney18, Sandra Goble18, Kevin K Lin18, James Sun19, Mitch Raponi18, Lindsey Rolfe18, Rebecca S Kristeleit20. 1. Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto M5G 2M9, Canada. Electronic address: amit.oza@uhn.ca. 2. Division of Medical Oncology, Vancouver Cancer Centre, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver V5N4E6, Canada. 3. Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, 119-129, 08035 Barcelona, Spain. 4. Sheba Medical Center, Emek HaEla St 1, 52621 Ramat Gan, Israel. 5. Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Glasgow G61 1QH, UK. 6. Department of Obstetrics and Gynecology, University of Washington, 1959 NE Pacific St, Seattle, WA 98195, USA. 7. GINECO, Centre Léon Bérard and University Claude Bernard, 28 rue Laennec, 69373 Lyon, France. 8. Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA. 9. The University of Texas MD Anderson Cancer Center, 1155 Herman Pressler Dr., CPB6.3590, Houston, TX 77030, USA. 10. The Ohio State University, James Cancer Center, M210 Starling Loving, 320 W 10th Ave, Columbus, OH 43210, USA. 11. GINECO, Gynecological Unit, Department of Medicine, Gustave Roussy Cancer Center and INSERM U981, 114 Rue Edouard-Vaillant, 94805 Villejuif, France. 12. 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. 13. Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Institut du cancer de Montréal, Department of Obstetrics and Gynecology, Université de Montréal, 1560 rue Sherbrooke Est, Montreal H2L 4M1, Canada. 14. Rocky Mountain Cancer Centers, 11750 W 2nd Pl #150, Lakewood, CO 80228, USA. 15. Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, CB2 0RE, UK. 16. David Geffen School of Medicine, University of California Los Angeles, 2825 Santa Monica Blvd, Suite 200, Santa Monica, CA 90404, USA. 17. Massachusetts General Hospital Cancer Center, Harvard Medical School, 185 Cambridge St, 5th floor, Boston, MA 02114, USA. 18. Clovis Oncology, Inc., 5500 Flatiron Parkway, Boulder, CO 80301, USA. 19. Foundation Medicine, Inc., 150 Second St, Cambridge, MA 02141, USA. 20. University College London Cancer Institute, 72 Huntley St, London WC1E 6BT, UK.
Abstract
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.
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.
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