Antonio Gonzalez-Martin, MD, PhD, director, Department of Medical Oncology, Clinica Universidad de Navarra, discusses new long-term progression-free survival (PFS) data from the phase 3 PRIMA trial (NCT02655016) in advanced ovarian cancer.


The randomized phase 3 trial investigated the efficacy of niraparib (Zejula) as a maintenance treatment for patients with stage III or IV ovarian cancer who had previously completed frontline platinum-based chemotherapy.


Updated findings presented at the 2022 ESMO Congress demonstrated that the administration of niraparib improved median progression-free survival (PFS) benefit when compared with placebo, confirming its sustained benefit in reducing the risk of disease progression or death, Gonzalez-Martin states. Compared with the data presented at the 2019 ESMO Congress, which had a median follow-up of 1.2 years, the median follow-up for the updated results was 3.5 years with a data cut-off in November 2021.


These new results show that niraparib reduced the risk of progression or death by 55% in patients with homologous recombination deficiency (HRD) and increased median PFS in that population from 11.2 months to 24.5 months. Similarly, median PFS in the overall population was prolonged from 8.2 months to 13.8 months, reducing the risk of progression or death by 34%, Gonzalez-Martin concludes.

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Antonio Gonzalez-Martin, MD, PhD, discusses new long-term progression-free survival data from the phase 3 PRIMA trial in advanced ovarian cancer.

Dr. González-Martín on Updated PFS Data From the PRIMA Trial in Advanced Ovarian Cancer

Antonio González-Martín, MD, co-director, Department of Medical Oncology, Clinica Universidad de Navarra, discusses the design of the phase III PRIMA trial (ENGOT-OV26/GOG-3012) in ovarian cancer.

The PRIMA study examined patients with high-grade serous or intermediate-grade stage III or IV cancer with microscopic residual disease after primary debulking surgery, or those who received neoadjuvant chemotherapy, regardless of their residual disease after interval debulking surgery, explains González-Martín. All patients were platinum-sensitive, meaning they achieved a complete response or partial response to chemotherapy.

Tissue was also collected for biomarker analysis and screening using the Myriad myChoice CDx assay to evaluate the homologous recombination deficiency (HRD) status of the tumor.

Patients were randomized 2:1 to receive either niraparib (Zejula) or placebo. Patients were randomized within 12 weeks of finishing the last cycle of chemotherapy. Niraparib was administered once daily for the duration of 36 months or until disease progression. At the initiation of the study, niraparib was administered at a fixed dose of 300 mg once daily, but the protocol was amended to allow patients to receive a lower dose of 200 mg, depending on their baseline body weight and platelet count. This was because data showed that individualized dosing may have a beneficial effect on niraparib-induced myelosuppression, explains González-Martín.

The primary end point of the study is progression-free survival, according to radiological RECIST criteria by blinded independent central review, says González-Martín. A hierarchal analysis of patients with HRD was also performed, concludes González-Martín.

Antonio González-Martín, MD, discusses the design of the PRIMA trial in ovarian cancer.

Dr. Gonzalez-Martin on the PRIMA Trial Design in Ovarian Cancer

Antonio Gonzalez-Martin, MD, co-director, Department of Medical Oncology, Clinica Universidad de Navarra, discusses the impact of the phase III PRIMA trial findings on clinical practice in advanced ovarian cancer.

The data from the PRIMA trial taken collectively with the data from phase III PAOLA-1 and VELIA trials are going to change the landscape of ovarian cancer, says Gonzalez-Martin. In PRIMA, niraparib (Zejula) maintenance led to a 38% reduction in the risk of progression or death versus placebo in patients with newly diagnosed, platinum-sensitive advanced ovarian cancer, regardless of biomarker status.

Notably, the PRIMA trial included patients for whom current treatment strategies are not as beneficial, adds Gonzalez-Martin, such as those who received neoadjuvant chemotherapy and bevacizumab (Avastin). These data represent a new standard of care in the overall population of patients with platinum-sensitive ovarian cancer, particularly those mentioned above who derived a significant benefit from niraparib maintenance, concludes Gonzalez-Martin.

Dr. Gonzalez-Martin on the Impact of the PRIMA Trial in Advanced Ovarian Cancer

Antonio Gonzalez-Martin, MD, co-director, Department of Medical Oncology, Clinica Universidad de Navarra, discusses the rationale for the phase III PRIMA trial investigating niraparib (Zejula) as maintenance therapy for patients with platinum-sensitive advanced ovarian cancer. 

The majority of patients with advanced ovarian cancer will relapse shortly after completing chemotherapy, says Gonzalez-Martin. Although there are maintenance therapy options, not all patients will benefit from them, he adds.

In the recurrent setting, niraparib has shown an improvement in progression-free survival (PFS) in platinum-sensitive patients regardless of 

 status or homologous recombination deficiency (HRD) status. Therefore, PRIMA was designed to evaluate niraparib as frontline maintenance therapy in patients with high-risk of relapse. 

In the overall population, the median progression-free survival (PFS) was 13.8 months in the niraparib arm compared with 8.2 months in the placebo arm (HR, 0.62; 95% CI, 0.50-0.76; 

 <.001). Notably, HRD-positive patients had a median PFS of 21.9 months with niraparib versus 10.4 months with placebo (HR, 0.43; 95% CI, 0.50-0.76; 

Antonio Gonzalez-Martin, MD, discusses the rationale for the phase III PRIMA trial investigating niraparib (Zejula) as maintenance therapy for patients with platinum-sensitive advanced ovarian cancer.
 

Dr. Gonzalez-Martin on Rationale for Phase III PRIMA Trial in Advanced Ovarian Cancer

Antonio Gonzalez-Martin, MD, co-director, Department of Medical Oncology, Clinica Universidad de Navarra, discusses the results of the phase III PRIMA trial in advanced ovarian cancer.

Data presented at the 2019 ESMO Congress demonstrated that frontline maintenance therapy with niraparib (Zejula) improved median progression-free survival (PFS) by 5.6 months versus placebo in patients with newly diagnosed, advanced platinum-sensitive ovarian cancer.

Investigators conducted a hierarchical analysis of patients with homologous recombination deficiency (HRD), which, if positive, would prompt analysis of the overall population, says Gonzalez-Martin. Among patients with HRD, the median PFS was 21.9 months with niraparib versus 10.4 months with placebo (HR, 0.43; 95% CI, 0.50-0.76; 

 <.001). The median PFS in the overall population was 13.8 months in the niraparib arm versus 8.2 months in the placebo arm, which translated to a 38% reduction in the risk of progression or death with the addition of the PARP inhibitor (HR, 0.62; 95% CI, 0.50-0.76; 

Antonio Gonzalez-Martin, MD

Articles

Dr. González-Martín on Updated PFS Data From the PRIMA Trial in Advanced Ovarian Cancer

Dr. Gonzalez-Martin on the PRIMA Trial Design in Ovarian Cancer

Dr. Gonzalez-Martin on the Impact of the PRIMA Trial in Advanced Ovarian Cancer

Dr. Gonzalez-Martin on Rationale for Phase III PRIMA Trial in Advanced Ovarian Cancer

Dr. Gonzalez-Martin on the Results of the PRIMA Trial in Ovarian Cancer