Cancer Treatment Today

On April 29, 2020, the FDA approved niraparib as a maintenance therapy for adults with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer with a complete or partial response to first-line platinum-based chemotherapy.
Niraparib’s latest approval is based on progression-free survival (PFS) data from the phase 3 PRIMA study (NCT02655016), which demonstrated a statistically significant improvement in both PRIMA’s homologous recombination deficiency (HRD) subset and overall population. The median PFS among patients with HRD was 21.9 months with niraparib compared with 10.4 months with placebo (HR, 0.43; 95% CI, 0.31-0.59; P <.0001). In the overall population, the median PFS was 13.8 months in the niraparib arm and 8.2 months in the placebo arm (HR, 0.62; 95% CI, 0.50-0.76; P <.0001).
The question is for combined use for later stage ovarian cancer and for treatment with avastin rather than maintenance. There is randomized trial evidence to support it.

The combination use of niraparib (Zejula) plus bevacizumab (Avastin) significantly improved clinical outcomes, compared with niraparib alone, in patients with recurrent ovarian cancer, according to updated survival data from the phase 2 portion of the AVANOVA trial (NSGO-AVANOVA2/ENGOT-OV24; NCT02354131).

The combination use of niraparib (Zejula) plus bevacizumab (Avastin) significantly improved clinical outcomes, compared with niraparib alone, in patients with recurrent ovarian cancer, according to updated survival data from the phase 2 portion of the AVANOVA trial (NSGO-AVANOVA2/ENGOT-OV24; NCT02354131) that were made available as part of the 2020 ASCO Virtual Scientific Program.1
The updated results continued to support earlier findings, with an observed 66% reduction in the risk of disease progression or death (HR, 0.34; 95% CI, 0.21-0.54). The median progression-free survival (PFS) in the bevacizumab arm was 12.5 months versus 5.5 months with niraparib alone.
Statistically significant improvements in time to second progression or death, or PFS2, was demonstrated in the bevacizumab/niraparib combination arm versus the niraparib control, with corresponding medians of 20.5 versus 15.7 months (HR, 0.56; 95% CI, 0.35-0.89; P = .015).
Other end points were also assessed, with a median follow-up of 24.7 months. Median time to first subsequent therapy was longer with the addition of bevacizumab at 14.3 months versus 7.2 months with niraparib alone (HR, 0.45; 95% CI, 0.29-0.70; P = .004). Similarly, time to second subsequent therapy was better with bevacizumab plus niraparib compared with the single-agent PARP inhibitor (21.8 vs17.3 months; HR, 0.56; 95% CI, 0.36-0.89; P = .014).
Although the study was not powered to detect differences in overall survival, there was a trend toward improvement with the niraparib plus bevacizumab combination versus niraparib alone, with medians of 29.4 months versus 27.8 months, respectively (HR, 0.75; 95% CI, 0.44-1.28).

CLINICAL / MEDICAL REFERENCES

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Hardesty MM, Fleming EL, Keeton E, et al. Phase II OVARIO study of niraparib + bevacizumab therapy in advanced ovarian cancer following front-line platinum-based chemotherapy with bevacizumab. Data made available as part of the virtual platform for the SGO 2020 Annual Meeting. Abstract 4. bit.ly/2RmcX8P.

PAOLA-1/ENGOT-ov25, Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394

Raza Mirza M, Nyvang G-B, Lund B, et al. Final survival analysis of NSGO-AVANOVA2/ENGOT-OV24: Combination of niraparib and bevacizumab versus niraparib alone as treatment of recurrent platinum-sensitive ovarian cancer-A randomized controlled chemotherapy-free study. J Clin Oncol. 2020;38(suppl 15):6012. doi:10.1200/JCO.2020.38.15_suppl.6012
Mirza MR, Åvall Lundqvist E, Birrer MJ, et al. Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial. Lancet Oncol. 2019;20(10):1409‐1419. doi:10.1016/S1470-2045(19)30515-7
NCCN Ovarian Cancer OV-6 2021