Real-World Study Supports Second-Line Maintenance Therapy With Niraparib in Recurrent Ovarian Cancer

Robert L. Coleman, MD, FACOG, FACS

A real-world study comparing second-line maintenance therapy with niraparib (Zejula), vs active surveillance (AS), led to improved overall survival (OS) among a BRCA gene wild-type (BRCAwt) population with recurrent ovarian cancer, according to data presented at the 2023 American Society of Clinical Oncology (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, gynecologic oncologist with Texas Oncology, a practice in The US Oncology Network, and Co-Director of the Gynecologic Oncology Group (GOG) Partners Foundatio, 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.

_Referencea:

_{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.}