Antonio González-Martín, MD, discusses the design and findings of the PRIMA trial in advanced ovarian cancer.
Antonio González-Martín, MD
Frontline maintenance therapy with niraparib (Zejula) represents a new standard of care among women with newly diagnosed, platinum-sensitive advanced ovarian cancer, according to data from the phase III PRIMA trial.
The data, which were presented at the 2019 ESMO Congress, demonstrated a 5.6-month extension in progression-free survival (PFS) with niraparib versus placebo in patients with newly diagnosed, advanced disease who achieved a complete or partial response (PR) to platinum-based chemotherapy.
In the overall population, the median PFS was 13.8 months with niraparib versus 8.2 months with placebo (HR, 0.62; 95% CI, 0.50-0.76; P <.001). Among those who tested positive for homologous recombination deficiency (HRD), the median PFS was 21.9 months versus 10.4 months with niraparib and placebo, respectively (HR, 0.43; 95% CI, 0.50-0.76; P <.001).
“The majority of patients with advanced ovarian cancer will relapse relatively quickly after completing platinum-based chemotherapy,” said lead study author Antonio González-Martín, MD. “We [can use olaparib (Lynparza)] as maintenance therapy; however, this approach is not suitable for every patient.”
“I believe PRIMA provides the clearest observation of the benefit of PARP inhibitors in the frontline maintenance setting, regardless of biomarker status,” said González-Martín. “It should be considered a new standard of care.”
In an interview with OncLive, González-Martín, co-director, Department of Medical Oncology, Clinica Universidad de Navarra, discussed the design and findings of the PRIMA trial in advanced ovarian cancer.
OncLive: What was the rationale for the PRIMA trial?
González-Martín: We know that the administration of niraparib in the recurrent platinum-sensitive setting leads to a significant prolongation in PFS, independent of BRCA status or HRD status. Therefore, we decided to run a trial exploring the same strategy, but in the frontline [maintenance setting] in patients with a high risk of relapse.
How was the study designed?
We included patients with high-grade serous or intermediate-[grade] stage III cancer with microscopic residual disease after primary debulking surgery, or those who received neoadjuvant chemotherapy for stage III disease, regardless of their residual disease after interval debulking surgery. We also included patients with stage IV disease. Importantly, these patients were platinum-sensitive, meaning they achieved a complete response or PR to chemotherapy.
We also collected tissue for biomarker analysis and screening. [We used] the Myriad myChoice CDx to evaluate the HRD status of the tumor. Patients were randomized 2:1 to receive either niraparib or placebo. Niraparib was administered once daily for 36 months or until disease progression. We started the treatment at the dose of 300 mg once daily. We amended the protocol to allow patients to receive 200 mg, depending on their baseline body weight and platelet count because we have data showing that individualized dosing may have a beneficial effect on niraparib-induced myelosuppression.
The endpoint of the study was PFS, according to radiological RECIST criteria by blinded independent central review. We would perform a hierarchical analysis in patients with HRD. If that analysis was positive, we would analyze the whole population.
What were the findings of the trial?
We saw a clear decrease in the risk of relapse in patients with HRD of 57%. The median PFS in that group of patients was 21.9 months with niraparib versus 10.4 months with placebo. We observed that close to 60% of patients at 18 months after randomization, which is approximately 2 years after starting chemotherapy, were still alive and progression free. Since the analysis in the HRD-positive population was positive, we analyzed the overall population. We observed a 38% reduction in the risk of relapse and a significant prolongation in medium PFS from 8.2 months with placebo to 13.8 months with niraparib. At 18 months after randomization, 42% of patients were alive and progression free.
What is the impact of these results on practice?
The data from PRIMA, taken collectively with the data from PAOLA-1 and VELIA, are going to change the landscape of ovarian cancer. We have several patients for whom we do not have good data with other drugs like bevacizumab (Avastin), such as patients who need to receive neoadjuvant chemotherapy. For those patients, we do not have good evidence of the impact of bevacizumab. Those patients represent two-thirds of the patients who were included in PRIMA in whom we saw a great benefit with niraparib. For those patients, niraparib is clearly another option. PRIMA has changed how we see and treat patients with ovarian cancer.
González-Martín A, Pothuri B, Vergote IB, et al. Niraparib therapy in patients with newly diagnosed advanced ovarian cancer (PRIMA/ENGOT-OV26/GOG-3012 study). Ann Oncol. 30(suppl 5; abstr LBA1). doi: 10.1093/annonc/mdz394.052.