Janssen has revealed updated results from the Phase III MAGNITUDE study, which show that a combination therapy including niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, slowed prostate cancer progression.
The drug was investigated in combination with abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) with or without specific homologous recombination repair (HRR) gene alterations, including BRCA mutations.
The results will be presented at the American Society of Clinical Oncology’s Genitourinary (ASCO GU) Cancers Symposium 2023.
In this second interim analysis of the study, the treatment combination in comparison to placebo and AAP at 26.8 months of median follow-up demonstrated a statistically significant prolongation in time to symptomatic progression (TSP).
It also showed continued consistent improvement of time-to-initiation of cytotoxic chemotherapy (TCC) in the HRR-positive population and a strong improvement in TSP for the BRCA subgroup of the HRR-positive population.
Updated radiographic progression free survival (rPFS) results were consistent with the primary analysis which showed statistically significant benefit in both the HRR-positive population and BRCA subgroup. Additionally, a trend toward improvement in overall survival (OS) was observed in the BRCA subgroup.
“Patients with HRR-positive mCRPC, especially those with BRCA mutations, are more likely to experience poor outcomes. Although additional follow-up for overall survival continues, it is encouraging to see a trend toward improvement in overall survival among patients with BRCA- positive mCRPC who received niraparib and AAP as compared to placebo and AAP,” said Kim Chi, Medical Oncologist at BC Cancer, Vancouver and principal investigator of the MAGNITUDE study.
High unmet need
Notably, in the BRCA subgroup (8.1 months additional follow-up), rPFS by central review demonstrated a consistent and clinically meaningful treatment effect favouring niraparib and AAP, with a median rPFS of 19.5 months compared with 10.9 months for placebo and AAP.
“A high unmet need remains for patients living with BRCA-mutated mCRPC. These findings underscore the importance of identifying patients with BRCA mutations to better inform treatment strategies and enable the right patients to receive add-on therapy with a PARP inhibitor,” said Mary Guckert, Vice President, Development Leader, Prostate Cancer, Janssen Research & Development.
Prostate cancer is the most common cancer in men across Europe. Patients with mCRPC and HRR gene alterations, of which BRCA mutations are the most common, are more likely to have aggressive disease, poor outcomes and a shorter survival time.
Marketing authorisation applications for the combination therapy are currently under review across several countries globally.
