Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer (2012) PDF

The n e w e ng l a n d j o u r na l of m e dic i n e original article Olaparib Maintenance Therapy...

The n e w e ng l a n d j o u r na l of m e dic i n e original article Olaparib Maintenance Therapy in Platinum-Sensitive Relapsed Ovarian Cancer Jonathan Ledermann, M.D., Philipp Harter, M.D., Charlie Gourley, M.B., Ph.D., Michael Friedlander, M.B., Ph.D., Ignace Vergote, M.D., Ph.D., Gordon Rustin, M.D., Clare Scott, M.B., Ph.D., Werner Meier, M.D., Ph.D., Ronnie Shapira-Frommer, M.D., Tamar Safra, M.D., Daniela Matei, M.D., Euan Macpherson, M.Sc., Claire Watkins, M.A., M.Sc., James Carmichael, M.D., and Ursula Matulonis, M.D. A BS T R AC T BACKGROUND From University College London, London Olaparib (AZD2281) is an oral poly(adenosine diphosphate [ADP]–ribose) polymerase (J.L.); Kliniken Essen Mitte, Essen (P.H.), inhibitor that has shown antitumor activity in patients with high-grade serous ovarian and Evangelisches Krankenhaus, Düssel- dorf (W.M.) — both in Germany; Univer- cancer with or without BRCA1 or BRCA2 germline mutations. sity of Edinburgh Cancer Research U.K. Centre, Edinburgh (C.G.); Prince of Wales METHODS Hospital, Randwick, NSW (M.F.), and Royal Melbourne Hospital, Parkville, NSW We conducted a randomized, double-blind, placebo-controlled, phase 2 study to eval- (C.S.) — both in Australia; University of uate maintenance treatment with olaparib in patients with platinum-sensitive, re- Leuven, Leuven, Belgium (I.V.); Mount lapsed, high-grade serous ovarian cancer who had received two or more platinum- Vernon Hospital, Northwood (G.R.), and AstraZeneca, Macclesfield (E.M., C.W., J.C.) based regimens and had had a partial or complete response to their most recent — both in the United Kingdom; Chaim platinum-based regimen. Patients were randomly assigned to receive olaparib, at a Sheba Medical Center, Tel Hashomer dose of 400 mg twice daily, or placebo. The primary end point was progression-free (R.S.-F.), and Tel Aviv Sourasky Medical Center, Tel Aviv (T.S.) — both in Israel; survival according to the Response Evaluation Criteria in Solid Tumors guidelines. Indiana University School of Medicine, Indianapolis (D.M.); and Dana–Farber RESULTS Cancer Institute, Boston (U.M.). Address reprint requests to Dr. Ledermann at the Of 265 patients who underwent randomization, 136 were assigned to the olaparib University College London (UCL) Cancer group and 129 to the placebo group. Progression-free survival was significantly Institute, UCL & UCL Hospitals Compre- longer with olaparib than with placebo (median, 8.4 months vs. 4.8 months from hensive Biomedical Research Centre, 90 Tottenham Court Rd., London W1T 4TJ, randomization on completion of chemotherapy; hazard ratio for progression or United Kingdom, or at j.ledermann@ctc death, 0.35; 95% confidence interval [CI], 0.25 to 0.49; P