PARP Inhibitor Rechallenge With Niraparib Plus Bevacizumab Is Feasible, Active in Recurrent Ovarian Cancer

Maintenance Niraparib/Bevacizumab in

Platinum-Sensitive Ovarian Cancer |

Image Credit: © LASZLO - stock.adobe.com

Maintenance niraparib (Zejula) plus bevacizumab (Avastin) demonstrated clinical activity in patients with platinum-sensitive, recurrent ovarian cancer who were previously treated with a PARP inhibitor, supporting the continued investigation of PARP inhibitor rechallenge for select patients who achieved good responses with prior platinum-based chemotherapy, according to Hyun-Woong Cho, MD, PhD.

Data from a subgroup analysis from the phase 2 KGOG 3056/NIRVANA-R trial (NCT047346655) presented at the 2025 SGO Annual Meeting on Women’s Cancer, revealed that at a data cutoff of June 1, 2024, the 6- and 12-month progression-free survival (PFS) rates, respectively, were 68% (95% CI, 55%-85%) and 46% (95% CI, 31%-68%). Notably, the median PFS was 11.5 months (95% CI, 7.9-not reached).1

“The results of the NIRVANA-R trial were quite good,” Cho said in an interview with OncLive®. “In the subgroup analysis, the 6-month PFS [rate] in particular was higher in patients with a long treatment-free interval from penultimate chemotherapy [as well as] those who achieved a CR with their most recent platinum-based chemotherapy [vs those who did not].”

During the interview, Cho highlighted the rationale for evaluating niraparib rechallenge plus bevacizumab as maintenance therapy in this patient population, key efficacy and safety data from NIRVANA-R study, and the top takeaways and the next steps for this research.

Cho is a member of the Department of Obstetrics and Gynecology at Korea University College of Medicine in Seoul.

OncLive: What prior data provided the impetus for evaluating niraparib rechallenge plus bevacizumab in platinum-sensitive, recurrent ovarian cancer in the NIRVANA-R study?

Cho: PARP inhibitor treatment as maintenance therapy is standard treatment in primary ovarian cancer and PARP inhibitor–naive, recurrent platinum-sensitive ovarian cancer. However, over half of patients experience recurrence within 5 years, and their response to subsequent chemotherapy is significantly decreased after PARP inhibitor therapy. The [phase 3] OReO/ENGOT-ov38 trial [NCT03106987] demonstrated that maintenance of olaparib rechallenge provided a significant improvement in PFS in this patient population but depends on whether double maintenance with niraparib plus bevacizumab this trial is beneficial for patients with platinum-sensitive ovarian cancer who were previously treated with a PARP inhibitor.

What was the design and methodology of this study?

The NIRVANA-R study [included patients with] non-mucinous histology; [those who received] penultimate chemotherapy over 12 months [prior to enrollment], and [those who achieved] complete remission [CR] or partial remission on their most recent chemotherapy. After enrollment, patients received niraparib plus bevacizumab as maintenance treatment until disease progression. The primary end point was 6-month PFS rate and a total of 44 patients were enrolled on this study.

What key efficacy and safety data were reported at the 2025 SGO Annual Meeting?

As of the data cutoff, the median follow-up period was 11.8 months. The primary end point estimate of the 6-month PFS rate was 68% and the median PFS was 11.5 months. This result can be compared to the previous OReO study, or multiple studies, which explored PARP inhibitor rechallenge strategies. The OReO study demonstrated a median PFS of 4.3 months, and the MOLTO study [NCT02855697] reported a median duration of PARP inhibitor rechallenge of 4.4 months.2,3

We already knew the safety profile of niraparib and bevacizumab. In this trial, no new safety signals were observed. [Toxicities leading to] treatment discontinuation were [reported in] 9.1% of patients, which is quite low.

What should your colleagues take away from this research?

This study evaluated double maintenance niraparib plus bevacizumab in [patients with] platinum-sensitive, recurrent ovarian cancer who were previously treated with a PARP inhibitor. The study showed promising activity, particularly in patients who had good responses to previous platinum-based chemotherapy. Based on the results of this study, we can try PARP inhibitor rechallenge in selected patients who had good responses to the prior platinum-based chemotherapy.

NIRVANA-R is a single-arm study, so we are trying to start a larger randomized trial to evaluate the efficacy of PARP inhibitor rechallenge [as a next step in research].

Disclosures: Cho reported receiving honoraria/expenses for consulting/advisory board participation from Chong Kin Dang, GSK, Merck, MSD, Onconic Therapeutics, Roche, and Takeda; research funding from Boryung, Chong Kun Dang, and Hanmi; and participating in clinical trials or contracted research with AbbVie, Corcept, DualityBio, GSK, Merck, Onconic Therapeutics, Regeneron, and Sutro Biopharma.

References

1. Cho HW, Park JY, Kim BG, et al. Phase 2 study of maintenance of niraparib rechallenge plus bevacizumab in patients with platinum-sensitive, recurrent ovarian cancer previously treated with a PARP inhibitor (KGOG 3056/NIRVANA-R). Presented at the 2025 Society of Gynecologic Oncology Annual Meeting on Women’s Cancer (SGO); Seattle, WA; March 14-17, 2025.
2. Pujade-Lauraine E, Selle F, Scambia G, et al. Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OReO/ENGOT-ov38): a phase IIIb trial. Ann Oncol. 2023;34(12):1152-1164. doi:10.1016/j.annonc.2023.09.3110
3. Morgan RD, Clamp AR, White DJ, et al. Multi-maintenance olaparib therapy in relapsed, germline BRCA1/2-mutant high-grade serous ovarian cancer (MOLTO): a phase II trial. Clin Cancer Res. 2023;29(14):2602-2611. doi:10.1158/1078-0432.CCR-22-3282