Patients with recurrent ovarian cancer who received Zejula (niraparib) maintenance therapy experienced longer progression-free survival, as well as more time without symptoms or toxicity compared with placebo, according to results from the phase 3 ENGOT-OV16/NOVA trial.
Patients with recurrent ovarian cancer who received Zejula (niraparib) maintenance therapy experienced more time without symptoms or toxicity compared with placebo, according to results from the phase 3 ENGOT-OV16/NOVA trial.
“This TWiST (time without symptoms or toxicity) analysis benefit means that patients treated with niraparib experienced more progression-free time without symptoms or toxicities due to nausea, vomiting, or fatigue compared to placebo,” Ursula A. Matulonis, M.D., director and chief of gynecologic oncology at Dana-Farber Cancer Institute, said during her presentation at the 50th SGO Annual Meeting, held March 16-19 in Honolulu, Hawaii.
In the multicenter, double-blind, randomized-controlled trial, patients with recurrent ovarian cancer who were in response to their last platinum-based chemotherapy were randomly assigned to receive either 300 mg of Zejula once daily as a maintenance treatment — including 138 patients in the germline BRCA-mutated cohort and 234 in the non-germline group – or placebo – made up of 65 patients in the germline BRCA-mutated cohort and 116 in the non-germline group.
The researchers aimed to assess whether the benefits of extending progression-free survival are offset by treatment-associated toxic effects that affect quality of life (QoL). The primary endpoint was progression-free survival, or the time from treatment to disease worsening.
Patients had to have histologically diagnosed high-grade serous or high-grade endometroid cancer, up to two prior lines or more of chemotherapy, and platinum-sensitive to their penultimate platinum therapy.
In previously published studies of the trial, treatment with maintenance Zejula significantly delayed disease progression compared to placebo, with progression-free survival of 21.0 versus 5.5 months, respectively, in the germline BRCA-mutated group and 9.3 versus 3.9 months in the non-germline BRCA-mutated group.
Quality of life remained stable through Zejula treatment and the pre-progression period compared with placebo.
In this portion of the trial, the researchers evaluated time without a certain level of three main symptoms: fatigue, nausea and vomiting. Average TWiST scores were calculated by subtracting the average time to toxicity from the average progression-free surival to partition the time to disease worsening in to two health states: time with toxicity and time without symptoms or toxicity.
“In this analysis, there were really two steps. The progression-free survival was extrapolated over 20 years. Survival curves were used to extrapolate progression-free survival of the NOVA data for Zejula versus placebo,” explained Matulonis. “The 20-year period was based on ovarian cancer clinical expert opinion and the biologic plausibility that a patient could be on PARP inhibitors for a long period of time. This approach has also been accepted by the (National Institute for Health and Care Excellence) as well as the Scottish medical authorities.”
“The second step was to estimate the time with toxicity from the number of days patients experience toxic effects due to grade 2 or higher nausea, vomiting and fatigue in the NOVA trial. (Side effects) were included post-randomization and prior to disease progression,” she added.
Treatment with Zejula compared with placebo in the germline BRCA-mutated and non- germline BRCA-mutated cohorts of the study resulted in an average TWiST benefit of 2.95 and 1.34 years, respectively — which was fourfold for those with germline BRCA-mutated disease and twofold for non- germline BRCA-mutated ovarian cancer.
In particular, treatment with Zejula resulted in an average progression-free survival benefit of 3.23 years and an average toxicity time of 0.28 years compared with placebo in germline BRCA-mutated patients, and an average progression-free survival benefit of 1.44 years and an average toxicity time of 0.10 years in non-germline BRCA-mutated patients.