PARP Combination Therapy Expands Treatment Indication in Prostate Cancer
FDA Approves First Targeted Regimen for Metastatic Castration-Sensitive Prostate Cancer Patients with a BRCA2 Gene Mutation
The U.S. Food and Drug Administration (FDA) has granted an expanded approval for a targeted combination therapy for patients with metastatic castration-sensitive prostate cancer (mCSPC) who harbor a BRCA2 gene mutation. This marks the first precision medicine approved specifically for this subset of patients.
The combination therapy is a dual-action tablet consisting of a PARP (poly-ADP ribose polymerase) inhibitor and an androgen-directed prostate cancer medication, used in conjunction with the corticosteroid prednisone to delay the progression of this aggressive form of prostate cancer.
The Phase 3 Amplitude study demonstrated that combining a PARP inhibitor with an androgen receptor pathway inhibitor could delay both radiographic and symptomatic disease progression in this patient population.
In the Amplitude trial, the new combination regimen, when added to androgen deprivation therapy (ADT), cut the risk of radiographic progression or death by 54% compared to the current standard of care (androgen-directed drug plus prednisone and ADT). The combination also extended the time to symptomatic progression by 59%.
Approximately 25% of mCSPC patients exhibit homologous recombination repair (HRR) gene alterations, including BRCA, which are linked to faster disease progression and poorer survival outcomes. While advances have been made in prostate cancer treatment, the company notes that nearly all patients eventually develop resistance to existing therapies, progressing to an incurable stage.
Exploratory analysis from the study indicated that the progression-free survival (PFS) benefit of the combination was notably larger in the BRCA-mutated subgroup, particularly in those with BRCA2 alterations. This narrowed approval mirrors the therapy’s initial nod in 2023 for BRCA-mutated metastatic castration-resistant prostate cancer (mCRPC)—a later disease stage.
The successful move into the earlier, castration-sensitive (mCSPC) treatment stage is a unique achievement among PARP inhibitors, strengthening the therapy’s position in the prostate cancer landscape.
