medwireNews: Men with metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) gene alterations could benefit from the addition of niraparib to first-line abiraterone acetate plus prednisone, suggest phase 3 trial data.
Adding the PARP inhibitor reduced the risk for radiographic progression or death by a significant 47% among patients with BRCA1 or BRCA2 mutations and by a significant 27% among those with alterations in any of the evaluated HRR genes, reported Kim Chi (University of British Columbia, Vancouver, Canada) at the 2022 ASCO Genitourinary Cancers Symposium in San Francisco, California, USA.
Gerhardt Attard tells us why he is excited about the results of the MAGNITUDE trial evaluating the upfront addition of niraparib to abiraterone acetate in men with metastatic castration-resistant prostate cancer harboring homologous recombination repair gene alterations (5:11).
“These study results support niraparib plus abiraterone as a new first-line treatment option for patients with metastatic CRPC and alterations in genes associated with homologous recombination repair,” he commented.
The double-blind MAGNITUDE study included 423 patients with alterations in specified HRR genes (ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, or PALB2) who had received no more than 4 months of abiraterone plus prednisone for mCRPC. Participants were randomly assigned to receive niraparib 200 mg/day or placebo together with standard-dose abiraterone plus prednisone.
The primary endpoint of independently assessed radiographic progression-free survival (PFS) in the 225 BRCA-mutated patients was significantly longer with the addition of niraparib rather than placebo to abiraterone–prednisone, at a median of 16.6 versus 10.9 months.
This was also the case for the full group of patients with any HRR gene alteration, at a median of 16.5 months with niraparib and 13.7 months with placebo.
In the full HRR-mutated group, supplementing abiraterone plus prednisone with niraparib instead of placebo was also associated with significant delays in the time to initiation of cytotoxic chemotherapy, symptomatic progression, and prostate-specific antigen (PSA) progression, with hazard ratios of 0.59, 0.69, and 0.57, respectively, in favor of the PARP inhibitor.
And the objective response rate was also nearly doubled among niraparib- compared with placebo-treated patients, at 60% versus 28%, as was the proportion of participants with a complete response, at 22% versus 11%.
At an interim analysis for overall survival, conducted at a median follow-up of 18.6 months, just 27% of the study population had died and therefore the data are immature.
The safety profile was as expected, said Chi. Just over two-thirds (67.0%) of patients in the niraparib group experienced an adverse event (AE) of grade 3 or 4, as did 46.4% of those in the placebo group. “This was largely driven by anemia, which was managed by drug interruptions, dose reductions, as well as supportive care,” he added.
A total of 10.8% of patients discontinued niraparib due to AEs, compared with 4.7% who discontinued placebo. There were 11 (5.2%) deaths due to AEs in the niraparib group and seven (3.3%) in the placebo group.
Of note, the MAGNITUDE investigators also evaluated niraparib in 233 mCRPC patients lacking HRR mutations. But the prespecified futility analysis using a composite endpoint of first event of PSA or radiographic progression found no benefit of adding the PARP inhibitor to abiraterone–prednisone in this population.
Chi therefore concluded that “MAGNITUDE highlights the importance of testing for HRR gene alterations in patients with metastatic CRPC to identify those individuals who optimally benefit from the combination of niraparib plus abiraterone.”
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ASCO Genitourinary Cancers Symposium; San Francisco, California, USA: 17–19 February 2022