A meta-analysis of data from the COU-AA-302 and ACIS clinical trials reveals that prior local therapy does not significantly compromise the treatment effects of first-line androgen receptor pathway inhibitors (ARPIs) in patients with metastatic castrate-resistant prostate cancer (mCRPC). The study, presented at the American Society for Radiation Oncology (ASTRO) 2024 Annual Meeting, suggests that oncologists can maintain confidence in using targeted therapies for mCRPC, irrespective of prior local therapy.
Study Details and Findings
The research, led by Omar Azem, MD, analyzed data from 2032 patients across the COU-AA-302 and ACIS trials. The aim was to determine if prior local therapy affected overall survival and radiographic progression-free survival (rPFS) in mCRPC patients treated with ARPIs and androgen deprivation therapy (ADT). The analysis included patients who received lone ADT (n = 527), ADT plus abiraterone (n = 1020), and apalutamide plus abiraterone (n = 485).
Among the patients who received prior local therapy (n = 1132), 47.1% had radiotherapy (RT), 22.3% had radical prostatectomy (RP), and 30.5% had RP plus RT. The investigators found no significant difference in the effect of prior local therapy on overall survival when comparing patients who received lone ADT (HR, 0.90; 95% CI, 0.69 – 1.17) or apalutamide plus abiraterone (HR, 1.29; 95% CI, 0.99 – 1.69) compared with ADT plus abiraterone.
Impact on Radiographic Progression-Free Survival
Local therapy modality was also not significantly associated with rPFS outcomes in ADT or ARPI-treated patients. The hazard ratios were as follows:
- RP: HR, 0.98; 95% CI, 0.81 – 1.18
- RT: HR, 0.99; 95% CI, 0.86 – 1.16
- RP plus RT: HR, 1.03; 95% CI, 1.03
Associations between local therapy modalities and overall survival with ADT or ARPIs were similarly insignificant among patients with mCRPC.
Implications for Clinical Practice
These findings contradict pre-clinical studies suggesting that prior local therapy could lead to neuroendocrine differentiation and compromise response to subsequent systemic therapies. The meta-analysis provides evidence that prior local therapy does not significantly impact the effectiveness of first-line ARPI treatment in mCRPC. "In this meta-analysis, we did not find any significantly compromised treatment effects from first line ARPI in patients who received prior local therapy," the investigators wrote. "Further, there was no significant association of prior local therapy modality with risk of radiographic progression or deaths, respectively."
