Niraparib Maintenance Treatment Improves Time Without Symptoms or Toxicity (TWiST) Versus Routine Surveillance in Recurrent Ovarian Cancer: A TWiST Analysis of the ENGOT-OV16/NOVA Trial

被引：27

作者：

Matulonis, Ursula A. ^{[1
]}

Walder, Lydia ^{[2
]}

Nottrup, Trine J. ^{[3
,4
]}

Bessette, Paul ^{[5
,6
]}

Mahner, Sven ^{[7
,8
]}

Gil-Martin, Marta ^{[9
,10
]}

Kalbacher, Elsa ^{[11
,12
]}

Ledermann, Jonathan A. ^{[13
,14
]}

Wenham, Robert M. ^{[15
]}

Woie, Kathrine ^{[16
,17
]}

Lau, Susie ^{[18
,19
]}

Marme, Frederik ^{[20
,21
]}

Casado Herraez, Antonio ^{[22
,23
]}

Hardy-Bessard, Anne-Claire ^{[24
,25
]}

Banerjee, Susana ^{[13
,26
,27
]}

Lindahl, Gabriel ^{[28
,29
]}

Benigno, Benedict ^{[30
]}

Buscema, Joseph ^{[31
]}

Travers, Karin ^{[32
]}

Guy, Holly ^{[2
]}

Mirza, Mansoor R. ^{[3
,4
]}

机构：

[1] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA

[2] FIECON Ltd, 3 Coll Yard,Lower Dagnall St, St Albans AL3 4PA, Herts, England

[3] Nord Soc Gynaecol Oncol, Copenhagen, Denmark

[4] Copenhagen Univ Hosp, Copenhagen, Denmark

[5] PMHC, Sherbrooke, PQ, Canada

[6] Univ Sherbrooke, Sherbrooke, PQ, Canada

[7] Arbeitsgemeinschaft Gynakol Onkol, Munich, Germany

[8] Univ Munich, Munich, Germany

[9] Grp Espanol Invest Canc Ovario, Barcelona, Spain

[10] IDIBELL, Inst Catala Oncol, Barcelona, Spain

[11] Grp Investigateurs Nationaux Etud Canc Ovariens, Besancon, France

[12] Univ Hosp Besancon, Besancon, France

[13] Natl Canc Res Inst, London, England

[14] UCL, Inst Canc, London, England

[15] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA

[16] Nord Soc Gynaecol Oncol, Bergen, Norway

[17] Haukeland Hosp, Bergen, Norway

[18] PMHC, Montreal, PQ, Canada

[19] Jewish Gen Hosp, Montreal, PQ, Canada

[20] Arbeitsgemeinschaft Gynakol Onkol, Heidelberg, Germany

[21] Univ Klinikum Heidelberg, Heidelberg, Germany

[22] Grp Espanol Invest Canc Ovario, Madrid, Spain

[23] Hosp Univ San Carlos, Madrid, Spain

[24] Grp Investigateurs Nationaux Etud Canc Ovariens, Paris, France

[25] Ctr Amoricain Oncol, Paris, France

[26] Royal Marsden NHS Fdn Trust, London, England

[27] Inst Canc Res, London, England

[28] Nord Soc Gynaecol Oncol, Linkoping, Sweden

[29] Linkoping Univ Hosp, Linkoping, Sweden

[30] Northside Hosp, Atlanta, GA USA

[31] Arizona Oncol, Tucson, AZ USA

[32] TESARO, Waltham, MA USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2019年 / 37卷 / 34期

关键词：

THERAPY; SURVIVAL;

D O I：

10.1200/JCO.19.00917

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PURPOSE This study estimated time without symptoms or toxicity (TWiST) with niraparib compared with routine surveillance (RS) in the maintenance treatment of patients with recurrent ovarian cancer. PATIENTS AND METHODS Mean progression-free survival (PFS) was estimated for niraparib and RS by fitting parametric survival distributions to Kaplan-Meier data for 553 patients with recurrent ovarian cancer who were enrolled in the phase III ENGOT-OV16/NOVA trial. Patients were categorized according to the presence or absence of a germline BRCA mutation-gBRCAmut and non-gBRCAmut cohorts. Mean time with toxicity was estimated based on the area under the Kaplan-Meier curve for symptomatic grade 2 or greater fatigue, nausea, and vomiting adverse events (AEs). Time with toxicity was the number of days a patient experienced an AE post-random assignment and before disease progression. TWiST was estimated as the difference between mean PFS and time with toxicity. Uncertainty was explored using alternative PFS estimates and considering all symptomatic grade 2 or greater AEs. RESULTS In the gBRCAmut and non-gBRCAmut cohorts, niraparib treatment resulted in a mean PFS benefit of 3.23 years and 1.44 years, respectively, and a mean time with toxicity of 0.28 years and 0.10 years, respectively, compared with RS. Hence, niraparib treatment resulted in a mean TWiST benefit of 2.95 years and 1.34 years, respectively, compared with RS, which is equivalent to more than four-fold and two-fold increases in mean TWiST between niraparib and RS in the gBRCAmut and non-gBRCAmut cohorts, respectively. This TWiST benefit was consistent across all sensitivity analyses, including modeling PFS over 5-, 10-, and 15-year time horizons. CONCLUSION Patients who were treated with niraparib compared with RS experienced increased mean TWiST. Thus, patients who were treated with niraparib in the ENGOT-OV16/NOVA trial experienced more time without symptoms or symptomatic toxicities compared with control. (C) 2019 by American Society of Clinical Oncology

引用

页码：3183 / 3191

页数：9

共 40 条

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Tinker, A. V.
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Harter, P.
Casado Herraez, A.
Follana, P.
Ledermann, J. A.
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Guy, H.
Mirza, M. R.
GYNECOLOGIC ONCOLOGY, 2019, 154 : 2 - 2
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JOURNAL OF CLINICAL ONCOLOGY, 2019, 37 (32) : 2968 - +

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