Antonio Gonzalez-Martin, MD, Department of Medical Oncology, Clinica Universidad de Navarra, Madrid, Spain, discusses the results of the PRIMA study which explored the safety and efficacy of niraparib therapy after response to platinum-based chemotherapy in patients with newly-diagnosed advanced ovarian cancer.

Transcript

My name is Antonio González Martín. I am medical oncologist at ClÌnica Universidad de Navarra in Madrid, Spain. I am the chair of the Spanish group for investigation in ovarian cancer. For 2 years I'm also the chair for ENGOT, which is the European Network of Gynecological Trials Group.

What I'm going to summarize is the results of the PRIMA study. The PRIMA study also called ENGOT-OV26/GOG-3012 was designed to test the efficacy and safety of niraparib therapy after response to platinum-based chemotherapy in patients with newly diagnosed advanced ovarian cancer, including patients with high risk of relapse.

The definition of high risk of relapse was based on stage IV or stage III with primary debulking surgery and microscopic residual disease or any stage III or IV patient that needed to receive neoadjuvant chemotherapy. Their histology was high-grade serous or endometrial histology.

Patients that fulfilled all this inclusion criteria were randomized 2:1 to niraparib or placebo. The primary end point of our trial was the progression-free survival. The analysis of progression-free survival was hierarchical first in the homologous combination deficient tumor population and then in the overall population.

We included 3 stratification factors in our trial. One was the use of neoadjuvant chemotherapy, yes or no, the best response to platinum-based chemotherapy, complete or partial, and also the status for homologous recombination that is deficient or proficient. A total of 333 patients were included and randomized in the trial.

Main characteristics of the patients were well-balanced across both arms. Approximately 35% of patients had a stage IV, 67% received neoadjuvant chemotherapy, and 31% achieved a partial response as best response to front-line chemotherapy. As you can imagine, the risk of relapse was high in this population.

Approximately half of the patients were homologous recombination deficient. Of those, 30% had the BRCA mutation. What we have demonstrated is that the addition of niraparib after front-line chemotherapy reduce their risk of relapse or death in the homologous recombination deficient population by 57%, with a hazard ratio of 0.43 and an increment in the median progression-free survival from 9.4 to 21.9 months.

According to our hierarchical analysis, we performed the analysis of the overall population and we showed that the addition of niraparib after front-line chemotherapy reduced the risk of relapse by 38% with a hazard ratio of 0.62.

Which is important to highlight is that this benefit was observed across all the subgroups that were predefined independently of the stage, the use of neoadjuvant chemotherapy, or the best response to platinum-based chemotherapy.

It should be also highlighted that this benefit was observed in patients that were BRCA-mutated and BRCA wild type in the group of homologous recombination deficient with a similar hazard ratio, 0.4 and 0.5. Also, in the homologous recombination proficient group, it has a ratio of 0.68.

In terms of safety, we observed a safety profile that is consistent with the data that we have for niraparib in the recurrent setting. Approximately 12% of patients needed to discontinue the therapy due to a treatment-emergent adverse event. Of those, the most common reason was thrombocytopenia in 4% of the cases.

It should be also highlighted that there were no deaths related to the drug and that we only observed one case of myelodysplastic syndrome.

In summary, what I can say is that niraparib added after standard front-line chemotherapy reduced significantly the progression-free survival for all the patients and also for patient that were homologous recombination deficient, proficient, and in the BRCA status.

The second great idea is that the niraparib reduced the risk in the group of patients with the highest risk of early progression as those that received neoadjuvant chemotherapy or do achieve only partial response after front-line chemotherapy.

Finally, no new safety signals were observed and the quality of life was maintained with niraparib. Based on all these observations, we believe that niraparib after first-line platinum-based chemotherapy should be considered the new standard of care for our patients.