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ENGOT-OV16/NOVA trial: Analysis shows improved TWiST with niraparib



– Patients with recurrent ovarian cancer who were treated with niraparib maintenance therapy experienced more time without symptoms or toxicities (TWiST) than did controls, according to an analysis of data from the pivotal phase 3 ENGOT-OV16/NOVA trial.

The mean 20-year TWiST benefit – defined in the current analysis as progression-free survival (PFS) without toxicity due to grade 2 or greater nausea, vomiting, or fatigue – was fourfold greater among women who were carriers of the 138 germline BRCA mutation (gBRCAmut) and received treatment with the poly(adenosine diphosphate-ribose) polymerase (PARP) 1/2 inhibitor than among the 65 similar women who received placebo. The TWiST benefit was about twofold greater among the 234 non-gBRCAmut carriers treated with niraparib than among the 116 who received placebo, Ursula A. Matulonis, MD, reported at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

The 10- and 5-year estimated mean improvement in TWiST in the groups also showed “very proportional effects that are similar to the 20-year data,” said Dr. Matulonis, chief of the division of gynecologic oncology at Dana-Farber Cancer Institute, and a professor of medicine at Harvard Medical School, Boston.

Dr. Ursula Matulonis

TWiSt is an “established methodology that partitions PFS ... based on time with toxicity and time without progression or toxicity." Mean TWiST is calculated as mean PFS minus mean toxicity, she explained.

In the ENGOT-OV16/NOVA study, women with recurrent ovarian cancer who received niraparib for maintenance after platinum-based therapy had significantly longer PFS, compared with patients who received placebo (21.0 vs. 5.5 months in gBRCAmut patients and 9.3 vs. 3.9 months in the non-gBRCAmut patients, respectively), she said (N Engl J Med 2016;75:2154-2164).

Quality of life (QOL) remained stable throughout niraparib treatment, according to another analysis of data from the trial published in 2018. (Lancet Oncology. Aug 1 2018;19[8]:1117-25).

The current analysis looked more closely at QOL by estimating mean TWiST in the treatment vs. control groups, she explained.

“Survival curves were used to extrapolate PFS ... over 20 years for both the gBRCAmut and non-gBRCAmut cohorts. The 20-year period was based on ovarian cancer clinical expert opinion and the biologic plausibility that patients could be on PARP inhibitors for a long period of time,” she said.

Time of toxicity was estimated based on the number of days patients experienced toxic effects due to grade 2 or higher nausea, vomiting, or fatigue during the NOVA trial.

The PFS benefit in treated vs. control subjects, respectively, was 3.23 years and 1.33 years in the gBRCAmut and non-gBRCAmut cohorts, and the mean toxicity time was 0.28 years and 0.10 years, for a mean TWiST benefit of 2.95 and 1.34 years, respectively.

“This TWiST benefit means that patients treated with niraparib experienced more progression-free time without symptoms or toxicities due to nausea, vomiting, or fatigue, compared with patients receiving placebo,” she concluded.

Dr. Matulonis is a consultant for 2X Oncology, Merck, Mersana, Fujifilm, Immunogen, and Geneos.

SOURCE: Matulonis U et al., SGO 2019: Abstract 1.

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