Niraparib Improves Outcomes in Patients With Stage III EOC, No Visible Residual Disease

Following first-line maintenance (1LM) treatment with niraparib monotherapy, patients with stage III epithelial ovarian cancer (EOC) and no visible residual disease (NVRD) after primary cytoreductive surgery (PCS) had significantly longer real-world time to next treatment (rwTTNT) and progression-free survival (rwPFS) than those with higher-risk prognostic factors for disease progression.¹

The authors of the recent Oncology and Therapy study explained that niraparib, a polymerase (PARP) inhibitor, was approved as an 1LM therapy for patients with advanced EOC based on results from the phase 3 PRIMA trial (NCT02655016)²; it demonstrated PFS improvement among patients who received 1LM niraparib monotherapy vs placebo. This trial included patients at higher risk for recurrence, meaning those with stage IV disease, inoperable stage III disease, or suboptimally debulked stage III disease, but excluded patients with stage III EOC who had NVRD after PCS.

In contrast, the PRIME trial (NCT03709316) included stage III patients with NVRD post PCS.³ It reported a longer median PFS in patients treated with niraparib compared with PRIMA. However, it remains unclear whether differences in patient inclusion criteria, particularly the exclusion or inclusion of higher-risk factors, influenced the magnitude of PFS benefit observed with niraparib across the 2 trials.¹

Therefore, the researchers conducted a retrospective observational study to evaluate the potential impact of excluding patients with stage III EOC with NVRD from the PRIMA trial by assessing real-world treatment outcomes in this population.

These findings suggest that excluding patients with stage III EOC and NVRD after PCS in the PRIMA trial may have underestimated niraparib’s benefits, emphasizing the importance of trial eligibility criteria in evaluating PARP inhibitors for this population. | Image Credit: luchschenF - stock.adobe.com

To do so, they used the Flatiron Health electronic health record (EHR)–derived deidentified database, which contains patient-level structured and unstructured data from about 280 cancer clinics, representing an estimated 800 sites of predominately community-based care in the US.

From this database, the researchers identified adult patients diagnosed with stage III/IV EOC who received 1L platinum-based chemotherapy and started niraparib 1LM monotherapy between January 1, 2017, and February 28, 2023. They placed eligible patients into either the PRIMA-like cohort, which included patients with EOC who had higher-risk prognostic factors for disease progression, or the stage III NVRD cohort, which included those with stage III EOC with NVRD after PCS.

The researchers defined the index date as 1LM niraparib monotherapy initiation. Also, follow-up was measured from the index date until death, the last EHR activity, or the end of the study, whichever came first.

The study’s main end points were rwTTNT and rwPFS, which the researchers estimated using Kaplan-Meier methods. They measured rwTTNT from the end date of 1L platinum-based chemotherapy to the second-line start date or death. Similarly, rwPFS was calculated from the end date of 1L platinum-based chemotherapy to the first documented real-world progression or death. A log-rank test was used to compare rwTTNT and rwPFS between the 2 cohorts.

Of the 11,698 patients diagnosed with OC in the database, 454 were eligible for the study. Consequently, the researchers assigned 390 to the PRIMA-like cohort and 63 to the stage III NVRD cohort. Those in the PRIMA-like cohort were older than the stage III NVRD cohort (aged >65 years: 60.0% vs 42.9%). Also, the median follow-up time was 14.9 months (IQR, 7.3-25.1) in the PRIMA-like cohort and 18.4 months (IQR, 9.3-29.1 months) in the stage III NVRD cohort.

The observed median rwTTNT in the stage III NVRD cohort (22.5 months; 95% CI, 17.3–not reached) was almost twice as long as that in the PRIMA-like cohort (11.7 months; 95% CI, 10.8-12.9; P < .001). Additionally, the observed median rwPFS in the stage III NVRD cohort (25.2 months; 95% CI, 12.6–not reached) was over twice as long as that in the PRIMA-like cohort (10.1 months; 95% CI, 9.1-11.9; P < .001).

Lastly, the researchers acknowledged their limitations. One was that the data set was limited to information recorded in patients’ EHRs because it was a retrospective database study. Therefore, their results are subject to the completeness of those records. Despite their limitations, they expressed confidence in their findings.

“Results from this real-world study suggest that the clinical benefit of niraparib may have been underestimated in the PRIMA trial because of the exclusion of patients with stage III EOC and NVRD after PCS and emphasize the importance of considering eligibility criteria when evaluating outcomes across trials that evaluate PARP inhibitors as 1LM in EOC,” the authors concluded.

References

1. Chase DM, Hanna M, Lim JT, et al. Niraparib as first-line maintenance therapy in patients with stage III ovarian cancer and no visible residual disease: AR1ZE real-world study. Oncol Ther. doi:10.1007/s40487-024-00318-y
2. González-Martín A, Pothuri B, Vergote I, et al. Progression-free survival and safety at 3.5 years of follow-up: results from the randomised phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib maintenance treatment in patients with newly diagnosed ovarian cancer. Eur J Cancer. 2023;189:112908. doi:10.1016/j.ejca.2023.04.024
3. Li N, Zhu J, Yin R, et al. Treatment with niraparib maintenance therapy in patients with newly diagnosed advanced ovarian cancer: a phase 3 randomized clinical trial. JAMA Oncol. 2023;9(9):1230–1237. doi:10.1001/jamaoncol.2023.2283