Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer

Jonathan Ledermann, Philipp Harter, Charlie Gourley, Michael Friedlander, Ignace Vergote, Gordon Rustin, Clare Scott, Werner Meier, Ronnie Shapira-Frommer, Tamar Safra, Daniela Matei, Euan Macpherson, Claire Watkins, James Carmichael, Ursula Matulonis

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Olaparib (AZD2281) is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor that has shown antitumor activity in patients with high-grade serous ovarian cancer with or without BRCA1 or BRCA2 germline mutations. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 2 study to evaluate maintenance treatment with olaparib in patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer who had received two or more platinumbased regimens and had had a partial or complete response to their most recent platinum-based regimen. Patients were randomly assigned to receive olaparib, at a dose of 400 mg twice daily, or placebo. The primary end point was progression-free survival according to the Response Evaluation Criteria in Solid Tumors guidelines. RESULTS: Of 265 patients who underwent randomization, 136 were assigned to the olaparib group and 129 to the placebo group. Progression-free survival was significantly longer with olaparib than with placebo (median, 8.4 months vs. 4.8 months from randomization on completion of chemotherapy; hazard ratio for progression or death, 0.35; 95% confidence interval [CI], 0.25 to 0.49; P<0.001). Subgroup analyses of progression-free survival showed that, regardless of subgroup, patients in the olaparib group had a lower risk of progression. Adverse events more commonly reported in the olaparib group than in the placebo group (by more than 10% of patients) were nausea (68% vs. 35%), fatigue (49% vs. 38%), vomiting (32% vs. 14%), and anemia (17% vs. 5%); the majority of adverse events were grade 1 or 2. An interim analysis of overall survival (38% maturity, meaning that 38% of the patients had died) showed no significant difference between groups (hazard ratio with olaparib, 0.94; 95% CI, 0.63 to 1.39; P = 0.75). CONCLUSIONS: Olaparib as maintenance treatment significantly improved progression-free survival among patients with platinum-sensitive, relapsed, high-grade serous ovarian cancer. Interim analysis showed no overall survival benefit. The toxicity profile of olaparib in this population was consistent with that in previous studies. (Funded by Astra- Zeneca; ClinicalTrials.gov number, NCT00753545.).

Original languageEnglish
Pages (from-to)1382-1392
Number of pages11
JournalNew England Journal of Medicine
Volume366
Issue number15
DOIs
StatePublished - Apr 12 2012

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Platinum
Ovarian Neoplasms
Placebos
Disease-Free Survival
Therapeutics
Random Allocation
olaparib
Confidence Intervals
Poly Adenosine Diphosphate Ribose
Germ-Line Mutation
Survival Analysis
Nausea
Vomiting
Fatigue
Anemia
Guidelines
Drug Therapy
Survival

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ledermann, J., Harter, P., Gourley, C., Friedlander, M., Vergote, I., Rustin, G., ... Matulonis, U. (2012). Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. New England Journal of Medicine, 366(15), 1382-1392. https://doi.org/10.1056/NEJMoa1105535

Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. / Ledermann, Jonathan; Harter, Philipp; Gourley, Charlie; Friedlander, Michael; Vergote, Ignace; Rustin, Gordon; Scott, Clare; Meier, Werner; Shapira-Frommer, Ronnie; Safra, Tamar; Matei, Daniela; Macpherson, Euan; Watkins, Claire; Carmichael, James; Matulonis, Ursula.

In: New England Journal of Medicine, Vol. 366, No. 15, 12.04.2012, p. 1382-1392.

Research output: Contribution to journalArticle

Ledermann, J, Harter, P, Gourley, C, Friedlander, M, Vergote, I, Rustin, G, Scott, C, Meier, W, Shapira-Frommer, R, Safra, T, Matei, D, Macpherson, E, Watkins, C, Carmichael, J & Matulonis, U 2012, 'Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer', New England Journal of Medicine, vol. 366, no. 15, pp. 1382-1392. https://doi.org/10.1056/NEJMoa1105535
Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. New England Journal of Medicine. 2012 Apr 12;366(15):1382-1392. https://doi.org/10.1056/NEJMoa1105535
Ledermann, Jonathan ; Harter, Philipp ; Gourley, Charlie ; Friedlander, Michael ; Vergote, Ignace ; Rustin, Gordon ; Scott, Clare ; Meier, Werner ; Shapira-Frommer, Ronnie ; Safra, Tamar ; Matei, Daniela ; Macpherson, Euan ; Watkins, Claire ; Carmichael, James ; Matulonis, Ursula. / Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. In: New England Journal of Medicine. 2012 ; Vol. 366, No. 15. pp. 1382-1392.
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AU - Scott, Clare

AU - Meier, Werner

AU - Shapira-Frommer, Ronnie

AU - Safra, Tamar

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