For patients with recurrent ovarian cancer that has been brought into remission with platinum-based chemotherapy, treatment with the drug niraparib can significantly prolong the time without symptoms or toxicity (TWiST), according to a new study led by researchers at Dana-Farber Cancer Institute.
The study, published online today by the Journal of Clinical Oncology, analyzed data from 553 participants in the phase III ENGOT-OV16/NOVA trial, which compared niraparib with a placebo in women with platinum-sensitive ovarian cancer who had received at least two courses of platinum-based chemotherapy. Results were calculated for participants with an inherited (germline) BRCA gene mutation and for those without such a mutation.
The analysis showed that the mean TWiST for women receiving niraparib maintenance therapy was more than four times higher than for patients receiving a placebo in the BRCA-mutant group and two times higher in the non-mutant group.
Niraparib (marketed as Zejula®) is a drug known as a PARP inhibitor, which undermines cancer cells by lowering their ability to repair damage to their DNA. It was approved by the Food and Drug Administration in 2017 as a maintenance treatment for women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are responding to platinum chemotherapy.
“When patients with recurrent ovarian cancer enter remission following platinum-based treatment, they now have the option to extend their progression-free survival with a PARP inhibitor,” said the study’s first author, Ursula Matulonis, MD, chief of the Division of Gynecologic Oncology at Dana-Farber.
TWiST is a statistical measure that provides an estimate of how long a patient is free of progressing disease and toxicity from treatment and therefore is likely to maintain a good quality of life. In this study, investigators first estimated the mean progression-free survival (PFS) and mean time with toxicity for patients treated with niraparib and those given a placebo. (Toxicity was defined as grade 2 or higher fatigue, nausea, or vomiting.) By calculating the difference in mean PFS and mean time with toxicity, researchers arrived at TWiST for each group.
A previous analysis of ENGOT-OV16/NOVA data showed that participants treated with niraparib went longer without disease progression than those who received a placebo. Said Matulonis, “It’s really important to demonstrate that, if we’re adding a maintenance therapy, we’re not significantly altering women’s quality of life.”
The senior author of study is Mansoor Mirza, MD, of Copenhagen University Hospital, in Denmark. Co-authors are Lydia Walder, MSc, and Holly Guy, MSc, of FIECON, St Albans, United Kingdom; Trine J. Nøttrup, MD, PhD of Copenhagen University Hospital, in Denmark; Paul Bessette, MD, of University of Sherbrooke, Quebec, Canada; Sven Mahner of University of Munich, Munich, Germany; Marta Gil-Martin, MD, of Institut Catala` d’Oncologia-IDIBELL, L’Hospitalet, Barcelona, Spain; Elsa Kalbacher, MD of University Hospital Besançon, Besançon, France; Jonathan A. Ledermann, MD, of National Cancer Research Institute and University College London Cancer Institute, London, United Kingdom; Robert M. Wenham, MD of H. Lee Moffitt Cancer Center; Kathrine Woie, MD, PhD, Haukeland University Hospital, Bergen, Norway; Susie Lau, MD, of Jewish General Hospital, Montreal, Quebec, Canada; Frederik Marme ́, MD, PhD, of Universitatsklinikum Heidelberg, Heidelberg, Germany; Antonio Casado Herraez, MD, PhD, Hospital Universitario San Carlos, Madrid, Spain; Anne-Claire Hardy-Bessard, MD, of Centre Amoricain D’Oncologie, Paris, France; Susana Banerjee, PhD, MA, of the National Cancer Research Institute and The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom; Gabriel Lindahl, MD, of Linkoping University Hospital, Linkoping, Sweden; Benedict Benigno, MD, of Northside Hospital, Atlanta, Ga.; Joseph Buscema, MD, of Arizona Oncology, Tucson, Ariz.; and Karin Travers, DSc, of TESARO, Waltham, Mass.