Chemo-Free Doublet Significantly Improved PFS in Recurrent Ovarian Cancer

Mansoor R. Mirza, MD

Mansoor R. Mirza, MD

The combination of niraparib (Zejula) and bevacizumab (Avastin) demonstrated a significant increase in progression-free survival (PFS) compared with niraparib alone in patients with platinum-sensitive recurrent ovarian cancer (PSROC), according to the results of the randomized ENGOT-OV24 trial.

Patients who received the chemotherapy-free doublet regimen had a median PFS of 11.9 months compared with 5.5 months in those who received niraparib alone. Those who had a prior platinum-free interval (PFS) of 6 to 12 months, or ≥12 months, derived a similar benefit from the combination treatment.

Niraparib and bevacizumab also proved active in patients with or without homologous recombination deficiency (HRD) and those with or withoutBRCAmutations, as reported at the 2019 ASCO Annual Meeting.¹

“[This study] is the first randomized trial to evaluate a chemotherapy-free combination of two established agents approved for use in recurrent ovarian cancer,” said Mansoor R. Mirza, MD, of Copenhagen University Hospital. “Compared with niraparib alone, the combination of niraparib and bevacizumab as definitive treatment for ovarian cancer significantly improved progression-free status regardless of HRD status or chemotherapy-free interval.

“The combination was well tolerated, and most patients remained on treatment until disease progression. No detrimental effect on quality of life was observed with combination therapy.”

A planned randomized phase III trial will compare the combination with standard-of-care therapy for PSROC, he added.

Platinum-based chemotherapy remains standard of care for PSROC but its use is limited by cumulative toxicity. In the phase III NOVA trial, niraparib maintenance following platinum-based chemotherapy significantly improved PFS without adversely affecting sensitivity to subsequent therapy.²Single-agent niraparib also proved active as definitive treatment for relapsed ovarian cancer.³

Mirza reported findings from the AVANOVA randomized phase II trial to evaluate PARP inhibition and anti-angiogenesis as alternative strategies to platinum-based chemotherapy. The rationale for the combination included observations that tumor hypoxia induced by anti-angiogenic agents enhanced PARP inhibition.

Investigators in the Nordic Society of Gynecologic Oncology enrolled patients with high-grade serous or endometrial PSROC and any number of prior lines of therapy. Patients were randomized to niraparib alone (300 mg once daily) or to the same dose of the PARP inhibitor plus bevacizumab 15 mg/kg every 3 weeks. Treatment continued until disease progression or development of unacceptable toxicity. The primary endpoint was investigator-assessed PFS in the intention-to-treat population.

Data analysis included 97 randomized patients, who had a median age of 66. About 40% of the patients had a PFI of 6 to 12 months and the interval exceeded 12 months in the rest. About 60% tested positive for HRD, and a third hadBRCA-mutant disease.

The primary analysis showed a 6.4-month improvement in median PFS with the combination, which represented a 65% reduction in the hazard for disease progression or death (P<.0001). The advantage conferred by the combination was similar for patients with a PFI of 6 to 12 month (11.3 vs 2.2 months,P= .0006) or >12 months (13.1 vs 6.1 months,&nbsp;P= .0062) and patients with HRD-positive tumors (11.9 vs 6.1 months,P= .0019) or HRD-negative tumors (11.3 vs 4.2 months, P= .0129). The combination offered a numerical advantage to patients with&nbsp;BRCA-mutant tumors (14.4 vs 9.0 months,P= .0947) and a statistically significant advantage to patients with&nbsp;BRCA-wild type tumors (11.3 vs 4.2 months,P=.0001).

The odds ratio (OR) for objective response quadrupled with the combination (60% vs 27%, OR 4.23,P= .001), and the odds of achieving disease control more than tripled (79% vs 53%, OR 3.36,P= .008).

Patients randomized to the combination had more adverse events, particularly nausea, vomiting, hypertension (associated with bevacizumab), peripheral neuropathy, and proteinuria. Severity was grade 1/2 in most cases except for a 20% incidence of grade &ge;3 hypertension.

An assessment of global health quality and quality of life over time showed no deterioration in either treatment group and no significant differences between the groups.

References

1. Mirza MR, Avall-Lundqvist E, Birrer MJ, et al. Combination of niraparib and bevacizumab versus niraparib alone as treatment of recurrent platinum-sensitive ovarian cancer. A randomized controlled chemotherapy-free study—NSGO-AVANOVA2/ENGOT-OV24.J Clin Oncol. 2019;37 (suppl; abstr 5505).
2. Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer.N Engl J Med.2016;375(22):2154-2164.
3. Moore KN, Secord AA, Geller MA, et al. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial.Lancet Oncol. 2019;20(5):636-648. doi: 10.1016/S1470-2045(19)30029-4.