Niraparib as Second-line Maintenance Demonstrates Real-world OS Benefit in Recurrent Ovarian Cancer

Second-line maintenance therapy with niraparib (Zejula) improved overall survival (OS) vs active surveillance (AS) in patients with recurrent BRCA wild-type ovarian cancer, according to data from a real-world study presented at the 2023 ASCO Annual Meeting.¹

“Overall, the study provided informative data on niraparib’s overall survival in BRCA wild type real world clinical practice population in the US receiving second-line maintenance niraparib compared with those under active surveillance,” Robert L. Coleman, MD, FACOG, FACS, a gynecologic oncologist and chief scientific officer for US Oncology Research, said in a presentation of the data at ASCO.

Real World Outcomes

For the second-line maintenance niraparib and AS groups, median follow-up was 16.8 months (range, 10.4-28.7) and 10.2 months (range, 4.1-23.7), respectively.

Treatment with second-line niraparib monotherapy led to a median OS of 28.12 months (95% CI, 22.54-43.24), compared with 21.45 months (95% CI, 14.72-27.04) with AS (HR, 0.63; 95% CI, 0.45-0.88). Further, 24-month OS rates were 58.2% (95% CI, 47.5%-67.6%) and 46.1% (95% CI, 33.6%-57.7%), respectively.

“Data distinguishing between germline and somatic BRCA mutations were not available; therefore, conclusions can only be made for BRCAwt patients,” Coleman et al concluded.

Real-World Study Background

In the trial presented at ASCO, Coleman and colleagues aimed to compare OS in the BRCAwt population of patients with recurrent ovarian cancer and who received second-line maintenance niraparib monotherapy or were under AS. The NOVA study-like population was comprised of patients with an ECOG performance status score of 0-1, known histology, and platinum-sensitive disease with 6 months or more between the end of first-line therapy and the start of second-line treatment.

The investigators used the US nationwide Flatiron Health de-identified electronic health record (EHR)-derived database, across approximately 280 cancer clinics, to identify patients diagnosed with epithelial ovarian cancer between January 1, 2011, and May 31, 2022, who completed second-line non-maintenance therapy between January 1, 2017, and March 2, 2022.

In total, 266 patients with BRCAwt disease received second-line maintenance therapy with niraparib (n = 123) or AS (n = 143).

Follow-up was measured from the index date, or the end of second-line non-maintenance therapy, until end of study, last activity, or death, whichever came first. The cloning approach to the trial included a target trial emulation cloned inverse probability of censoring weighting methodology.

Overall, in the niraparib and AS cohorts, 23.6% and 34.3% of patients, respectively, were age 75 years or older, while 26.0% and 16.8% reported an EHR value of race other than White. Furthermore, the majority of patients reported with stage III disease (53.7% vs 60.8%, respectively) and serous ovarian cancer (79.7% vs 81.1%).

In addition, after the index rate date, patients in the niraparib and AS cohorts received at least 1 or more oncologist-defined, rule-based line of therapy (61.8% vs 69.9%, respectively), including 20.3% and 21.0% who received 3 or more.

NOVA Trial

“Patients with advanced ovarian cancer typically have a high rate of recurrence and a poor prognosis the 5-year survival rate is approximately 30% for patient with advance disease,” Coleman et al wrote.

Therefore, in the randomized, double-blind, placebo-controlled phase 3 NOVA trial (NCT01847274) aimed to determine the efficacy of second-line niraparib monotherapy in patients with platinum-sensitive recurrent ovarian cancer who had an ECOG performance status of 0-1 and known histology.^2-3

In the trial, second-line niraparib maintenance demonstrated an improvement in progression-free survival (PFS) among those with germline-BRCA (gBRCA) mutation, indicating its benefit beyond progression, Coleman et al wrote.

While PFS improved, OS, a secondary end point in the trial, with niraparib demonstrated a trend toward improved survival in patients with a gBRCA-mutation based on adjusted analyses (median OS, 40.9 months vs 38.1 months; HR, 0.85; 95% CI, 0.61-1.20). However, Coleman et all noted that “analyses were confounded by imbalances in post-progression therapy by treatment arm in gBRCA mutation and non-gBRCA mutation cohorts.”

Further, secondary end points, such as PFS2, chemotherapy-free interval, and time to first and second subsequent therapy also demonstrated benefit from niraparib in both cohorts.

References

1. Coleman RL, Perhanidis J, Kalilani L, Zimmerman NM, Golembesky A, Moore KN. Real-world overall survival in second-line maintenance niraparib monotherapy vs active surveillance in BRCA wild-type patients with recurrent ovarian cancer. J Clin Oncol. 2023;41(16):5592-5592. doi:.10.1200/JCO.2023.41.16_suppl.5592.
2. Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. N Engl J Med. 2016;375:2154-2164. doi:10.1056/NEJMoa1611310.
3. González-Martín A, Pothuri B, Vergote I, et al. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019;381:2391-2402. doi:10.1056/NEJMoa1910962.