Conditional PFS Rates Support Benefit of Niraparib in Ovarian Cancer

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In patients with ovarian cancer whose tumors were homologous recombination deficient (HRD), treatment with niraparib (Zejula) led to durable conditional progression-free survival (cPFS) rates compared with placebo up to 4 years post randomization, according to results from the PRIMA/ENGOT-OV26/GOG-3012 study (NCT02655016). Findings were presented at the European Society for Medical Oncology Gynaecological Cancers Congress 2023.¹

Investigators reported on the cPFS, which represents the probability that patients remain free of progression and death at a predefined time after reaching a predefined landmark standpoint.

“In the subset of patients who survived either 1 or 2 years post randomization in the PRIMA study, we evaluated the probability of being alive and progression free for an additional 2 years,” Antonio González-Martín, MD, PhD, director of the Department of Medical Oncology at Clínica Universidad de Navarra, Madrid, Spain, said during a presentation of the data.

In the HRD population, cPFS at 2 years was 51% in the niraparib arm vs 29% in the placebo arm. The 1-year landmark cPFS was 62% vs 50%, respectively, and the 2-year landmark cPFS was 74% vs 60%.

The standard PFS rate at 3 years was 44% in the niraparib arm and 23% in the placebo arm in the HRD population. At 4 years, the rate for PFS was 38% for niraparib and 17% for placebo. Estimates for 2-year cPFS rates were higher at each additional year of PFS.

In the overall population, cPFS from the 1-year landmark was 54% in the niraparib arm vs 46% in the placebo arm and the 2-year landmark was 67% in the niraparib arm vs 64% in the placebo arm. Standard PFS rate at 3 years was 29% vs 18%, respectively, and at 4 years the standard PFS rate was 24% vs 14%, respectively. “Again, the estimates for 2-year cPFS rates were higher at each additional year of PFS,” González-Martín said.

The phase 3 PRIMA/ENGOT OV26/GOG 3012 study evaluated niraparib as frontline maintenance treatment in patients with newly diagnosed advanced ovarian cancer after a response to frontline platinum-based chemotherapy. Study participants were at high risk for disease progression: Thirty-five percent had stage IV disease, 99.6% of patients with stage III disease had residual disease post primary debulking surgery, 67% received neoadjuvant chemotherapy, and only 31% achieved a partial response to first-line chemotherapy.

In the primary analysis of the study,² investigators reported that niraparib significantly extended PFS compared with placebo in patients with HRD tumors (HR, 0.43; 95% CI, 0.31-0.59; P < .001). In the overall population, researchers noted a 38% chance of death (HR, 0.62; 95% CI, 0.50-0.76; P < .001).

Updated long-term PFS and safety evaluation at data cutoff of November 2021 suggested that patients treated with niraparib were more likely to be free of progression and death at 4 years than those who received placebo in both the HRD population (38% in the niraparib arm vs 17% in the placebo arm) and overall population (24% vs 14%, respectively).³ In this update, adverse events were manageable and consistent with the primary analysis.

“Conditional PFS is a clinically relevant measure that may be useful for patients with advanced ovarian cancer, characterized by high rates of progression in the first 2 years post diagnosis,” González-Martín said.

The findings suggest that patients who are free from death and progression at the 1- and 2-year landmarks had a high probability of being alive and progression-free 2 years later. “This illustrates the long-term effect of niraparib and supports its use as a first-line maintenance therapy,” GonzálezMartín concluded.

REFERENCES

1. González-Martín A, Pothuri B, Vergote I, et al. PRIMA/ ENGOT OV26/GOG 3012 study: long term conditional PFS. Ann Oncol. 2023;8(suppl 1):100811. doi:10.1016/esmoop/ esmoop100811

2. González-Martín A, Pothuri B, Vergote I, et al; PRIMA/ ENGOT-OV26/GOG-3012 Investigators. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2019;381(25):2391-2402. doi:10.1056/NEJMoa1910962

3. González-Martín AJ, Pothuri B, Vergote IB, et al. PRIMA/ ENGOT-OV26/GOG-3012 study: updated long-term PFS and safety. Ann Oncol. 2022;33(suppl 7):S789. doi:10.1016/j. annonc.2022.07.658