Immature data suggest it may also confer additional disease progression and survival benefits

Niraparib maintenance therapy lengthened time to first subsequent therapy (TFST), compared with placebo, among patients with advanced ovarian cancer who had previously responded to platinum-based chemotherapy, according to an analysis of secondary outcomes in the PRIMA/ENGOT-OV26/GOG-3012 trial.

“Niraparib provided a long-term benefit across a broad population of patients with ovarian cancer,” said lead author Sileny N. Han, MD, PhD, of University Hospitals Leuven, Leuven, Belgium, in her presentation of the data during a Society of Gynecologic Oncology (SGO) webinar that took place on April 29, 2020. “Treatment benefits persist beyond the first progression. For time to first subsequent therapy, there were significant advantages in favor of niraparib, both for the overall population and in patients with both homologous recombination deficient [HRd] and homologous recombination proficient [HRp] tumors. Although progression-free survival 2 [PFS2] and overall survival [OS] survival data are immature, the data numerically favor niraparib maintenance therapy versus placebo in all biomarker subgroups.”

The findings were to be presented at the SGO 2020 annual meeting, planned to take place in Toronto, Canada from March 28 to 31. The conference was cancelled due to the Covid-19 pandemic, but a series of webinars of several studies intended to be presented at the conference were subsequently made available online.

In the overall population, TFST was greater with niraparib, compared with placebo, in all patients (13.7 versus 3.7 months), with a hazard ratio (HR) of 0.65 (95% CI 0.52-0.80). This was also the case for patients who were HRd (HR 0.46; 95% CI 0.33-0.64) and HRp (HR 0.64; 95% CI 0.46-0.90).

Preliminary data numerically favor niraparib with respect to PFS2, which evaluated time to progression on second-line treatment, although the PFS2 event rates were low, so definitive conclusions cannot be drawn.

In the overall population, 37% of patients continued to receive niraparib, compared with 28% of those on placebo, at the time of the primary analysis. Among the patients who had progressed, a greater proportion in the placebo group than the niraparib group received subsequent treatment (51% versus 41%). Most of the time, this subsequent treatment was platinum-based.

Preliminary OS data also numerically favored niraparib, with a 2-year OS of 84% with niraparib versus 77% with placebo. In the HRd population, the equivalent proportions are 91% and 85%. In the HRp population, they are 81% and 59%.

PRIMA/ENGOT-OV26/GOG-3012 was a phase III, double-blind trial in which 733 patients with newly diagnosed advanced ovarian, primary peritoneal, or fallopian tube cancer with a complete or partial response to first-line platinum-based chemotherapy were randomized to treatment with either niraparib (n = 487) or placebo (n = 246) once daily for 36 months or until disease progression. The primary endpoint of the study was PFS, as assessed by a blinded independent central review, overall and based on homologous recombination status. As previously reported, PFS was greater in niraparib-treated patients, with a hazard ratio (HR) of 0.62 (95% CI 0.502-0.755; P < 0.0001). Another SGO presentation demonstrated that PFS was significantly greater regardless of BRCA mutation or homologous recombination status.

Key secondary endpoints of the trial were TFST and PFS2. “For all efficacy endpoints, measurements began at time of randomization, which was within the first 12 weeks of completing the first-line platinum-based chemotherapy,” explained Han during her presentation of the data. “PFS is defined as time until disease progression or death. TFST was defined as time from randomization to time when the patient received the next chemotherapy regimen for the first recurrence. PFS2 was defined as the time from randomization to the time when the patient progressed on second-line treatment.”

“Realize that a lot of these data are immature, but if you look at some of the more mature data, TFST, you understand how these variables are interrelated,” said Thomas J. Herzog, MD, of the University of Cincinnati Cancer Center in Cincinnati, Ohio in a comment on the study during the SGO webinar. “It makes sense that they would be interrelated. The [TFST] is very similar to what you see for the overall treatment effect… and then if you break it down to then looking at first subsequent treatment, PFS2, and even an early look at OS, you see a [similar] treatment effect. Interestingly, you do not see where [the confidence interval] crosses 1 [for TFST] for the group that was HRp. So, that’s interesting data.”

  1. Patients with advanced ovarian cancer who responded to platinum-based chemotherapy had a longer time to subsequent therapy if they received maintenance treatment with niraparib, compared with placebo.

  2. Preliminary data suggest niraparib maintenance therapy may also improve overall survival and time to progression on second-line therapy.

Alison Palkhivala, Contributing Writer, BreakingMED™

Han reports receiving support from the Leuvens Kanker Instituut.

Herzog reports being on advisory boards for and/or receiving honoraria/reimbursement from Genentech, Caris, Tesaro, Clovis, Johnson&Johnson, and AstraZeneca.

Cat ID: 445

Topic ID: 78,445,730,445,692,357,693,192,356