• Ursula A Matulonis, Lydia Walder, Trine J Nøttrup, Paul Bessette, Sven Mahner, Marta Gil-Martin, Elsa Kalbacher, Jonathan A Ledermann, Robert M Wenham, Kathrine Woie, Susie Lau, Frederik Marmé, Casado Herraez Antonio A Grupo Español de Investigación en Cáncer de Ovario and Hospital Universitario San Carlos, Madrid, Spain., Anne-Claire Hardy-Bessard, Susana Banerjee, Gabriel Lindahl, Benedict Benigno, Joseph Buscema, Karin Travers, Holly Guy, and Mansoor R Mirza.
• Dana-Farber Cancer Institute, Boston, MA.
• J. Clin. Oncol. 2019 Dec 1; 37 (34): 3183-3191.

PurposeThis 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 MethodsMean 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.ResultsIn 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.ConclusionPatients 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.

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