Recent Clinical Trial Data in mCRPC
An expert discusses recent trial data showing that combining radium-223 with enzalutamide modestly improves outcomes in metastatic castration-resistant prostate cancer (mCRPC) with bone metastases—highlighting the necessity of bone-modifying agents to reduce fracture risk—while results from the TRITON3 trial underscore the greater efficacy of PARP inhibitors such as rucaparib when used early and in combination for BRCA-mutated patients.
A recent phase 3 trial, conducted in Europe, evaluated the benefit of combining radium-223 with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) mCRPC and bone metastases. The study focused on asymptomatic or mildly symptomatic individuals and included 446 patients randomized randomly assigned to either enzalutamide alone or in combination with radium. Results showed a modest improvement in radiographic progression-free survival, from 16 to 19 months, with a 30% reduction in risk of progression or death. Overall survival also improved by about seven 7 months with the addition of radium, suggesting a meaningful, though moderate, benefit.
An important takeaway from this trial was the critical role of bone-modifying agents in reducing fracture risk. Early in the trial, a significant number of fractures occurred in patients who received radium without concurrent bone-strengthening therapy. This finding reinforces the importance of always including bone-modifying agents in treatment plans for mCRPC, particularly when using bone-targeted therapies. These results support the use of radium as a partner to enzalutamide in appropriately selected patients but also highlight the need for careful management of skeletal health.
In parallel, data from the TRITON3 trial explored PARP inhibitor monotherapy using rucaparib in patients with mCRPC who had BRCA1, BRCA2, or ATM mutations and had progressed on androgen receptor pathway inhibitors (ARPI) therapy. Patients were randomized randomly assigned to receive rucaparib or standard treatments, including chemotherapy or an alternate ARPI. Among patients with BRCA-positive patients disease, rucaparib extended progression-free survival by about five 5 months, whereas the benefit in ATM mutation carriers was minimal. These findings emphasize that while monotherapy with PARP inhibitors is effective post-progression, greater benefits are typically seen when used earlier in the disease course in combination with ARPIs. Early combination therapy remains the preferred strategy for patients with HRR homologous recombination repair mutations.
