A larger population of patients with newly diagnosed advanced ovarian cancer may be able to benefit from niraparib maintenance therapy, with an improved safety profile, according to phase III data presented at the 2022 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer.¹

Results of the phase III PRIME study showed that maintenance therapy with the PARP (poly [ADP-ribose] polymerase) inhibitor niraparib led to significantly longer progression-free survival vs placebo in patients with newly diagnosed advanced ovarian cancer (24.8 months vs 8.3 months; P < .001). Unlike the PRIMA study, however, which led to the approval of niraparib as maintenance therapy, the PRIME study also enrolled patients with stage III ovarian cancer who had no residual disease after primary debulking surgery.²

Ning Li, MD

“The PRIME study demonstrated that in patients with newly diagnosed ovarian cancer, niraparib maintenance therapy provided a significant improvement in progression-free survival compared with placebo, regardless of biomarker status and postoperative residual disease status,” said lead study author, Ning Li, MD, of the Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing. “The safety profile of niraparib was also improved with the individualized starting dose prospectively applied to all patients.”

Background

As Dr. Li explained, niraparib has been approved globally as maintenance therapy after a complete or partial response to first-line, platinum-based chemotherapy, according to the results of the PRIMA study. This trial demonstrated that niraparib maintenance therapy conferred progression-free survival benefit to patients with advanced ovarian cancer compared with placebo, regardless of biomarker status.

However, the PRIMA study did not include patients with stage III disease who achieved R0 resection (ie, no gross residual disease after primary debulking surgery). Moreover, individualized starting dosing based on baseline body weight and platelet count to improve the safety profile of niraparib was used in just about 35% of patients in the PRIMA trial.

“Whether different initial dose will affect efficacy needs to be verified by prospective study,” said Dr. Li.

Study Methods

The double-blind, placebo-controlled PRIME study enrolled patients with advanced ovarian cancer with high-grade serous or endometrioid tumors who had a complete or partial response to first-line, platinum-based chemotherapy. Patients were randomly assigned to receive niraparib or placebo and were stratified by germline BRCA mutation, homologous recombination–deficiency (HRD) status, receipt of neoadjuvant chemotherapy, and response to first-line chemotherapy.

The treatment was continued for 36 months or until disease progression or unacceptable toxicities. An individualized starting dose of 200 or 300 mg daily was applied to all patients according to their body weight and platelet count.

The primary endpoint was progression-free survival by blinded independent central review in the intention-to-treat population.

Progression-Free Survival Three Times Longer

A total of 381 patients were included in the PRIME trial (254 were given niraparib and 127 were given placebo). As of September 30, 2021, the median follow-up was 27.5 months, and 40% of the niraparib group and 22.5% of the placebo group remained on treatment.

The baseline characteristics were well balanced between the study arms. Approximately 71% of patients randomly assigned to niraparib had stage III ovarian cancer, 83% had a complete response to chemotherapy, and 33.3% carried germline BRCA mutations.

In the intent-to-treat population, niraparib maintenance therapy reduced the risk for disease progression or death by 55%. Median progression-free survival in the niraparib group (24.8 months) was nearly three times longer than that in the placebo group (8.3 months).

“Subgroup analysis showed that the progression-free survival benefit of niraparib vs placebo was consistent across all prespecified subgroups,” stated Dr. Li. “Niraparib provided a clinical benefit regardless of germline BRCA–mutation status. Of note, the median progression-free survival has still not been reached in the germline BRCA–mutation subgroup.”

Niraparib reduced the risk for disease progression or death by 60% in patients with germline BRCA mutation and by 52% in patients without germline BRCA mutations.

“In the non-germline BRCA–mutated subgroup, this study again confirmed the progression-free survival benefit of niraparib regardless of HRD status,” said Dr. Li. He noted similar hazard ratios in both HRD (hazard ratio [HR] = 0.48) and homologous recombination–proficient subgroups (HR = 0.41).

In the intent-to-treat population, overall survival data are still immature, but there is a trend in favor of niraparib. Niraparib also significantly prolonged the time to first subsequent anticancer therapy compared with placebo (29.2 months vs 11.9 months).

Safety Profile

The safety profile of niraparib was manageable and consistent with the PARP inhibitor class. The most common adverse events associated with niraparib were hematologic and gastrointestinal. Compared with the PRIMA study, however, the rates of treatment interruptions, dose reductions, and treatment discontinuations were significantly decreased in the PRIME study, with an individualized starting dose applied to the entire population.

Treatment-related adverse events leading to treatment interruptions decreased from 79.5% in the PRIMA trial to 62.7% in the PRIME trial; dose reductions and treatment discontinuations dropped from 70.9% to 20.4% and from 12.0% to 6.7%, respectively. According to Dr. Li, the improved safety profile of niraparib with an individualized starting dose might translate into better efficacy.

“Results from the PRIME study continue to support niraparib monotherapy as standard of care after first-line platinum-based chemotherapy regardless of biomarker status,” Dr. Li concluded. 

DISCLOSURE: Dr. Li reported no conflicts of interest.

REFERENCES

1. Li N, Zhu J, Yin R, et al: Efficacy and safety of niraparib as maintenance treatment in patients with newly diagnosed advanced ovarian cancer using an individualized starting dose (PRIME study): A randomized, double-blind, placebo- controlled, phase 3 trial. 2022 SGO Annual Meeting on Women’s Cancer. Abstract 244. Presented March 19, 2022.

2. González-Martín A, Pothuri B, Vergote I, et al: Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 381:2391-2402, 2019.