Kathleen Moore1, Nicoletta Colombo1, Giovanni Scambia1, Byoung-Gie Kim1, Ana Oaknin1, Michael Friedlander1, Alla Lisyanskaya1, Anne Floquet1, Alexandra Leary1, Gabe S Sonke1, Charlie Gourley1, Susana Banerjee1, Amit Oza1, Antonio González-Martín1, Carol Aghajanian1, William Bradley1, Cara Mathews1, Joyce Liu1, Elizabeth S Lowe1, Ralph Bloomfield1, Paul DiSilvestro1. 1. From the Stephenson Cancer Center at the University of Oklahoma, Oklahoma City (K.M.); University of Milan-Bicocca, European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico, Milan (N.C.), and Fondazione Policlinico Universitario A. Gemelli IRCCS Università Cattolica, Rome (G.S.) - both in Italy; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea (B.-G.K.); Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona (A. Oaknin), and M.D. Anderson Cancer Centre Madrid, Madrid (A.G.-M.) - both in Spain; University of New South Wales Clinical School, Prince of Wales Hospital, Randwick, Australia (M.F.); St. Petersburg City Oncology Dispensary, St. Petersburg, Russia (A. Lisyanskaya); Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens, Paris (A.F., A. Leary), Institut Bergonié, Comprehensive Cancer Center, Bordeaux (A.F.), and Gustave-Roussy Cancer Campus, Villejuif (A. Leary) - all in France; the Netherlands Cancer Institute, Amsterdam (G.S.S.); Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh (C.G.), the Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London (S.B.), and AstraZeneca, Cambridge (R.B.) - all in the United Kingdom; Princess Margaret Cancer Centre, Toronto (A. Oza); Memorial Sloan Kettering Cancer Center, New York (C.A.); Froedtert and the Medical College of Wisconsin, Milwaukee (W.B.); Women and Infants Hospital, Providence, RI (C.M., P.D.); Dana-Farber Cancer Institute, Boston (J.L.); and AstraZeneca, Gaithersburg, MD (E.S.L.).
Abstract
BACKGROUND:Most women with newly diagnosed advanced ovarian cancer have a relapse within 3 years after standard treatment with surgery and platinum-based chemotherapy. The benefit of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib in relapsed disease has been well established, but the benefit of olaparib as maintenance therapy in newly diagnosed disease is uncertain. METHODS: We conducted an international, randomized, double-blind, phase 3 trial to evaluate the efficacy of olaparib as maintenance therapy in patients with newly diagnosed advanced (International Federation of Gynecology and Obstetrics stage III or IV) high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian-tube cancer (or a combination thereof) with a mutation in BRCA1, BRCA2, or both ( BRCA1/2) who had a complete or partial clinical response after platinum-based chemotherapy. The patients were randomly assigned, in a 2:1 ratio, to receive olaparib tablets (300 mg twice daily) or placebo. The primary end point was progression-free survival. RESULTS: Of the 391 patients who underwent randomization, 260 were assigned to receiveolaparib and 131 to receive placebo. A total of 388 patients had a centrally confirmed germline BRCA1/2 mutation, and 2 patients had a centrally confirmed somatic BRCA1/2 mutation. After a median follow-up of 41 months, the risk of disease progression or death was 70% lower with olaparib than with placebo (Kaplan-Meier estimate of the rate of freedom from disease progression and from death at 3 years, 60% vs. 27%; hazard ratio for disease progression or death, 0.30; 95% confidence interval, 0.23 to 0.41; P<0.001). Adverse events were consistent with the known toxic effects of olaparib. CONCLUSIONS: The use of maintenance therapy with olaparib provided a substantial benefit with regard to progression-free survival among women with newly diagnosed advanced ovarian cancer and a BRCA1/2 mutation, with a 70% lower risk of disease progression or death with olaparib than withplacebo. (Funded by AstraZeneca and Merck; SOLO1 ClinicalTrials.gov number, NCT01844986 .).
RCT Entities:
BACKGROUND: Most women with newly diagnosed advanced ovarian cancer have a relapse within 3 years after standard treatment with surgery and platinum-based chemotherapy. The benefit of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib in relapsed disease has been well established, but the benefit of olaparib as maintenance therapy in newly diagnosed disease is uncertain. METHODS: We conducted an international, randomized, double-blind, phase 3 trial to evaluate the efficacy of olaparib as maintenance therapy in patients with newly diagnosed advanced (International Federation of Gynecology and Obstetrics stage III or IV) high-grade serous or endometrioid ovarian cancer, primary peritoneal cancer, or fallopian-tube cancer (or a combination thereof) with a mutation in BRCA1, BRCA2, or both ( BRCA1/2) who had a complete or partial clinical response after platinum-based chemotherapy. The patients were randomly assigned, in a 2:1 ratio, to receive olaparib tablets (300 mg twice daily) or placebo. The primary end point was progression-free survival. RESULTS: Of the 391 patients who underwent randomization, 260 were assigned to receive olaparib and 131 to receive placebo. A total of 388 patients had a centrally confirmed germline BRCA1/2 mutation, and 2 patients had a centrally confirmed somatic BRCA1/2 mutation. After a median follow-up of 41 months, the risk of disease progression or death was 70% lower with olaparib than with placebo (Kaplan-Meier estimate of the rate of freedom from disease progression and from death at 3 years, 60% vs. 27%; hazard ratio for disease progression or death, 0.30; 95% confidence interval, 0.23 to 0.41; P<0.001). Adverse events were consistent with the known toxic effects of olaparib. CONCLUSIONS: The use of maintenance therapy with olaparib provided a substantial benefit with regard to progression-free survival among women with newly diagnosed advanced ovarian cancer and a BRCA1/2 mutation, with a 70% lower risk of disease progression or death with olaparib than with placebo. (Funded by AstraZeneca and Merck; SOLO1 ClinicalTrials.gov number, NCT01844986 .).
Authors: Kalindi Parmar; Bose S Kochupurakkal; Jean-Bernard Lazaro; Zhigang C Wang; Sangeetha Palakurthi; Paul T Kirschmeier; Chunyu Yang; Larissa A Sambel; Anniina Färkkilä; Elizaveta Reznichenko; Hunter D Reavis; Connor E Dunn; Lee Zou; Khanh T Do; Panagiotis A Konstantinopoulos; Ursula A Matulonis; Joyce F Liu; Alan D D'Andrea; Geoffrey I Shapiro Journal: Clin Cancer Res Date: 2019-08-13 Impact factor: 12.531