Niraparib in Combination With Abiraterone Acetate and Prednisone vs Abiraterone Acetate and Prednisone for Treatment of Metastatic Prostate Cancer

PracticeUpdate: What did the MAGNITUDE trial investigate?

Dr. Sartor: The MAGNITUDE trial looked at first-line metastatic CRPC patients. And they allowed up to four months of prior abiraterone prior to the randomization. There were two cohorts. There was one cohort that was homologous recombination repair mutated. And these are genes such as BRCA1, BRCA2, CHEK2, FANCA, PALB2, etcetera. And interestingly, they over-enrolled the BRCA1 and BRCA2 subset, and I think that could have some importance.

In addition, there was a non-mutated, non-homologous recombination repair mutated subset that was planned. And again, in each case, the treatment was with abiraterone, and there was a randomization to niraparib, a PARP inhibitor, or placebo. rPFS was the primary endpoint by central review.

PracticeUpdate: How were the results planned and interpreted for this trial?

Dr. Sartor: The first analysis that was planned was in the BRCA1 and BRCA2 mutated subset. And here, the rPFS, by central review, was clearly positive, hazard ratio of 0.53. So, the addition of niraparib to abiraterone was favorable as compared to abiraterone plus placebo on the rPFS endpoint.

Now, the next analysis was looking at the rPFS in the non-BRCA homologous recombination repair mutated. And here, the hazard ratio was 0.99. In other words, there really was no effect.

In the cohort that looked at non-mutated homologous recombination repair pathways, again, there was no effect. And actually, that particular arm was closed early for futility. They used a progression endpoint, the combined radiographic progression and PSA progression in the futility analysis for the non-mutated patients. And by the way, it was only rPFS as the endpoint, no PSA progression in the patients’ mutations.

PracticeUpdate: What are your conclusions on the MAGNITUDE trial?

Dr. Sartor: What would I conclude? I would conclude that abiraterone plus niraparib is better in the BRCA1- and BRCA2-mutated patients. By the way, they did not break out BRCA1 and BRCA2, but looking those together, I think it certainly makes sense. But in the non-homologous recombination repair, non-BRCA, but still homologous recombination repair mutated, there did not appear to be an rPFS benefit. And if you went to the patients with no mutation, there was no benefit of adding niraparib.

I think we need to see more data, particularly with overall survival. We do not have any overall survival right now. But I think this is likely to be a positive study in the BRCA-mutated patients, but not likely to be a positive study in those that have non-BRCA homologous recombination repair mutations. And definitely, because of the futility, the niraparib does not add to abiraterone in patients with no HRR mutations.

So, overall, an interesting and provocative finding presented by Kim Chi at ASCO GU. And we look forward to learning more about this trial with longer follow-up. Thank you.