In a study reported in the Journal of Clinical Oncology, Ursula A. Matulonis, MD, and colleagues found that niraparib maintenance therapy was associated with increased time without symptoms or toxicity (TWiST) vs routine surveillance among women with platinum-sensitive recurrent ovarian cancer in the phase III ENGOT-OV16/NOVA trial.
Ursula A. Matulonis, MD
Study Details
In the trial, patients with partial or complete response to platinum-based chemotherapy were randomly assigned 2:1 to receive niraparib 300 mg per day or placebo until disease progression. The trial showed significantly improved progression-free survival with niraparib treatment both in patients with a germline BRCA mutation and in those without a mutation.
In the current analysis, mean progression-free survival was estimated for niraparib and routine surveillance by fitting parametric survival distributions to Kaplan-Meier data for 553 patients enrolled in the trial. Patients were categorized into germline BRCA–mutant (n = 138 patients treated with niraparib patients, n = 65 routine surveillance) and non–germline BRCA-mutant (n = 234 niraparib, n = 116 routine surveillance). Mean time with toxicity was estimated from area under Kaplan-Meier curves for symptomatic grade ≥ 2 fatigue, nausea, and vomiting; time with toxicity was the number of days a patient experienced an adverse event after random assignment and before disease progression. TWiST was estimated as the difference between mean progression-free survival and time with toxicity.
TWiST Outcomes
In the germline BRCA–mutant cohort, treatment with niraparib was associated with mean progression-free survival of 4.14 years and mean time with toxicity of 0.31 years, yielding a mean TWiST of 3.83 years. Routine surveillance was associated with mean progression-free survival of 0.91 years and mean time with toxicity of 0.03 years, yielding a mean TWiST of 0.88 years. Thus, niraparib treatment was associated with a mean TWiST benefit of 2.95 years.
KEY POINTS
- Time without symptoms or toxicity (TWiST) was calculated as the difference between mean progression-free survival and mean time with toxicity.
- Niraparib was associated with a TWiST benefit in both germline BRCA–mutant and non–germline BRCA-mutant cohorts.
In the non–germline BRCA-mutant cohort, niraparib was associated with mean progression-free survival of 2.59 years and mean time with toxicity of 0.13 years, yielding a mean TWiST of 2.46 years. Routine surveillance was associated with mean progression-free survival of 1.14 years and mean time with toxicity of 0.02 years, yielding a mean TWiST of 1.12 years. Thus, niraparib treatment was associated with a mean TWiST benefit of 1.34 years.
The investigators concluded, “Patients who were treated with niraparib compared with [routine surveillance] 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.”
Dr. Matulonis, of Dana-Farber Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Tesaro, a GSK company. For full disclosures of the study authors, visit jco.ascopubs.org.
