Long-term efficacy, tolerability and overall survival in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer treated with maintenance olaparib capsules following response to chemotherapy

被引：154

作者：

Friedlander, Michael ^{[1
]}

Matulonis, Ursula ^{[2
]}

Gourley, Charlie ^{[3
]}

du Bois, Andreas ^{[4
]}

Vergote, Ignace ^{[5
]}

Rustin, Gordon ^{[6
]}

Scott, Clare ^{[7
]}

Meier, Werner ^{[8
]}

Shapira-Frommer, Ronnie ^{[9
]}

Safra, Tamar ^{[10
,11
]}

Matei, Daniela ^{[12
]}

Shirinkin, Vadim ^{[13
]}

Selle, Frederic ^{[14
,15
]}

Fielding, Anitra ^{[16
,17
]}

Lowe, Elizabeth S. ^{[17
]}

McMurtry, Emma L. ^{[16
]}

Spencer, Stuart ^{[16
]}

Rowe, Philip ^{[16
]}

Mann, Helen ^{[16
]}

Parry, David ^{[16
]}

Ledermann, Jonathan ^{[18
]}

机构：

[1] Univ New South Wales, Prince Wales Hosp, Clin Sch, Randwick, NSW, Australia

[2] Dana Farber Canc Inst, Boston, MA 02115 USA

[3] Western Gen Hosp, Canc Res UK Edinburgh Ctr, Edinburgh, Midlothian, Scotland

[4] Kliniken Essen Mitte, Essen, Germany

[5] Univ Leuven, Leuven Canc Inst, Leuven, Belgium

[6] Mt Vernon Hosp, Northwood, Middx, England

[7] Royal Melbourne Hosp, Parkville, Vic, Australia

[8] Univ Dusseldorf, Dusseldorf, Germany

[9] Chaim Sheba Med Ctr, Tel Hashomer, Israel

[10] Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel

[11] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel

[12] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA

[13] Orenburg Reg Clin Oncol Dispensary, Orenburg, Russia

[14] Grp Hosp Diaconesses Croix St Simon, Paris, France

[15] GINECO Grp, Paris, France

[16] AstraZeneca, Cambridge, England

[17] AstraZeneca, Gaithersburg, MD USA

[18] UCL, Canc Inst, London, England

来源：

BRITISH JOURNAL OF CANCER | 2018年 / 119卷 / 09期

关键词：

DOUBLE-BLIND; END-POINTS; THERAPY; PHASE-2; MUTATION; TRIAL;

D O I：

10.1038/s41416-018-0271-y

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND: In Study 19, maintenance monotherapy with olaparib significantly prolonged progression-free survival vs placebo in patients with platinum-sensitive, recurrent high-grade serous ovarian cancer. METHODS: Study 19 was a randomised, placebo-controlled, Phase II trial enrolling 265 patients who had received at least two platinum-based chemotherapy regimens and were in complete or partial response to their most recent regimen. Patients were randomised to olaparib (capsules; 400 mg bid) or placebo. We present long-term safety and final mature overall survival (OS; 79% maturity) data, from the last data cut-off (9 May 2016). RESULTS: Thirty-two patients (24%) received maintenance olaparib for over 2 years; 15 (11%) did so for over 6 years. No new tolerability signals were identified with long-term treatment and adverse events were generally low grade. The incidence of discontinuations due to adverse events was low (6%). An apparent OS advantage was observed with olaparib vs placebo (hazard ratio 0.73, 95% confidence interval 0.55. 0.95, P = 0.02138) irrespective of BRCA1/2 mutation status, although the predefined threshold for statistical significance was not met. CONCLUSIONS: Study 19 showed a favourable final OS result irrespective of BRCA1/2 mutation status and unprecedented longterm benefit with maintenance olaparib for a subset of platinum-sensitive, recurrent ovarian cancer patients.

引用

页码：1075 / 1085

页数：11

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