Matthew Powell, MD: Niraparib had the indication for maintenance after 2 prior lines of chemotherapy in patients who have responded to their first chemotherapy with a platinum-based therapy, and then had a complete or partial response after their second line of therapy. This is in all-comers. There was a high statistical significance in all groups showing benefit in each the germline BRCA patients, homologous recombination patients, and those who were wild-type and HRD-negative.

Oliver Dorigo, MD, PhD: The NOVA trial was a large trial that evaluated the efficacy and safety of the PARP inhibitor, niraparib, in patients with platinum-sensitive recurrent ovarian cancer. Those patients had to have at least a partial or complete response to prior platinum-based chemotherapy. Niraparib was started within 8 weeks after administration of the last course of chemotherapy, and then patients were followed over time. It was a randomized controlled trial. Patients were randomized in a 2-to-1 fashion to either receive niraparib or placebo. What was found in this trial is that those patients on niraparib had a significantly prolonged progression-free survival.

The observation in this trial was stopped at 24 months, and we still have to await the overall survival data, which are still maturing. I think one of the key elements of this trial was that all patients—

regardless of mutations in BRCA1 and BRCA2 and regardless of the degree of homologous recombination deficiency, which was likewise tested in those patients’ tumors—had a benefit from niraparib. The efficacy was still the greatest in those patients who had BRCA1 and BRCA2 mutations, either in the germline or in the tumor, but there was still a significant difference in those patients who lacked those mutations in BRCA1 and BRCA2. This data prompted the FDA to approve niraparib regardless of BRCA1 and BRCA2 mutation status, and that’s why we do not have a companion diagnostic required for the use of niraparib.

Niraparib in the NOVA trial certainly had a very scientific and detailed follow-up of those patients on the trial. Radiographic assessment using mostly CT scans was done every 8 weeks for the first 14 cycles and every 12 weeks following the fourteenth cycle. CA-125 likewise was assessed very frequently. Those measurements are rather standard. The niraparib trial had, I think, very close follow-up. They also followed patients for the development of symptoms and prompted radiographic studies or further evaluation if patients reported symptoms outside of the regular scheduled radiographic assessments. So, I think the study design is a very careful study design. It’s done very scientifically and allowed the investigators to really diagnose recurrences as early as they could. In that sense, I think we can trust the data from the niraparib trial as being rather solid and not having missed recurrences that might have happened earlier.

Whitney S. Graybill, MD, MS: In the NOVA trial, there were 3 primary efficacy populations: BRCA germline-positive; BRCA germline-negative; and BRCA negative, HRD-positive. In all 3 of these primary populations, there was a significant improvement in progression-free survival. In addition, there was a population of germline BRCA-negative, HRD-negative patients. That was an exploratory population. And even in this population of patients, there was a significant increase in progression-free survival of around 3 months.

I think this is really important because it’s really the first time it’s expanded the use of a PARP inhibitor outside of patients with a BRCA mutation or HRD positivity. It really showed an improvement in progression-free survival in all patient populations. And because of these results, patients can go on this drug without needing germline testing or HRD testing.

Matthew Powell, MD: There were 203 patients who had a BRCA1 and BRCA2 gene mutation on this study, and that group showed the highest benefit with over 21 months of progression-free survival in the group receiving niraparib versus 5.5 months in the group receiving placebo. These were highly statistically significant differences.

Transcript Edited for Clarity