PMID- 31518175 OWN - NLM STAT- MEDLINE DCOM- 20200622 LR - 20201201 IS - 1527-7755 (Electronic) IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 37 IP - 34 DP - 2019 Dec 1 TI - 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. PG - 3183-3191 LID - 10.1200/JCO.19.00917 [doi] AB - 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. FAU - Matulonis, Ursula A AU - Matulonis UA AD - Dana-Farber Cancer Institute, Boston, MA. FAU - Walder, Lydia AU - Walder L AD - FIECON, Ltd, St Albans, United Kingdom. FAU - Nottrup, Trine J AU - Nottrup TJ AD - Nordic Society of Gynaecological Oncology and Copenhagen University Hospital, Copenhagen, Denmark. FAU - Bessette, Paul AU - Bessette P AD - PMHC and University of Sherbrooke, Sherbrooke, Quebec, Canada. FAU - Mahner, Sven AU - Mahner S AD - Arbeitsgemeinschaft Gynakologische Onkologie and University of Munich, Munich, Germany. FAU - Gil-Martin, Marta AU - Gil-Martin M AD - Grupo Espanol de Investigacion en Cancer de Ovario and Institut Catala d'Oncologia-IDIBELL, L'Hospitalet, Barcelona, Spain. FAU - Kalbacher, Elsa AU - Kalbacher E AD - Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens and University Hospital Besancon, Besancon, France. FAU - Ledermann, Jonathan A AU - Ledermann JA AD - National Cancer Research Institute and University College London Cancer Institute, London, United Kingdom. FAU - Wenham, Robert M AU - Wenham RM AD - H. Lee Moffitt Cancer Center, Tampa, FL. FAU - Woie, Kathrine AU - Woie K AD - Nordic Society of Gynaecological Oncology and Haukeland University Hospital, Bergen, Norway. FAU - Lau, Susie AU - Lau S AD - PMHC and Jewish General Hospital, Montreal, Quebec, Canada. FAU - Marme, Frederik AU - Marme F AD - Arbeitsgemeinschaft Gynakologische Onkologie and Universitatsklinikum Heidelberg, Heidelberg, Germany. FAU - Casado Herraez, Antonio AU - Casado Herraez A AD - Grupo Espanol de Investigacion en Cancer de Ovario and Hospital Universitario San Carlos, Madrid, Spain. FAU - Hardy-Bessard, Anne-Claire AU - Hardy-Bessard AC AD - Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens and Centre Amoricain D'Oncologie, Paris, France. FAU - Banerjee, Susana AU - Banerjee S AD - National Cancer Research Institute and The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom. FAU - Lindahl, Gabriel AU - Lindahl G AD - Nordic Society of Gynaecological Oncology and Linkoping University Hospital, Linkoping, Sweden. FAU - Benigno, Benedict AU - Benigno B AD - Northside Hospital, Atlanta, GA. FAU - Buscema, Joseph AU - Buscema J AD - Arizona Oncology, Tucson, AZ. FAU - Travers, Karin AU - Travers K AD - TESARO: A GSK Company, Waltham, MA. FAU - Guy, Holly AU - Guy H AD - FIECON, Ltd, St Albans, United Kingdom. FAU - Mirza, Mansoor R AU - Mirza MR AD - Nordic Society of Gynaecological Oncology and Copenhagen University Hospital, Copenhagen, Denmark. LA - eng SI - ClinicalTrials.gov/NCT01847274 PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190916 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (BRCA1 Protein) RN - 0 (BRCA1 protein, human) RN - 0 (BRCA2 Protein) RN - 0 (BRCA2 protein, human) RN - 0 (Indazoles) RN - 0 (Piperidines) RN - 0 (Poly(ADP-ribose) Polymerase Inhibitors) RN - HMC2H89N35 (niraparib) SB - IM MH - BRCA1 Protein/genetics MH - BRCA2 Protein/genetics MH - Disease Progression MH - Drug Administration Schedule MH - Female MH - Germ-Line Mutation MH - Humans MH - Indazoles/*administration & dosage/adverse effects MH - Maintenance Chemotherapy MH - *Neoplasm Recurrence, Local MH - Ovarian Neoplasms/*drug therapy/genetics/mortality/pathology MH - Piperidines/*administration & dosage/adverse effects MH - Poly(ADP-ribose) Polymerase Inhibitors/*administration & dosage/adverse effects MH - Progression-Free Survival MH - Randomized Controlled Trials as Topic MH - Risk Assessment MH - Risk Factors MH - Time Factors PMC - PMC6881097 EDAT- 2019/09/14 06:00 MHDA- 2020/06/23 06:00 PMCR- 2020/12/01 CRDT- 2019/09/14 06:00 PHST- 2019/09/14 06:00 [pubmed] PHST- 2020/06/23 06:00 [medline] PHST- 2019/09/14 06:00 [entrez] PHST- 2020/12/01 00:00 [pmc-release] AID - 1900917 [pii] AID - 10.1200/JCO.19.00917 [doi] PST - ppublish SO - J Clin Oncol. 2019 Dec 1;37(34):3183-3191. doi: 10.1200/JCO.19.00917. Epub 2019 Sep 16.