Key clinical point: Ipilimumab significantly improved overall survival (OS) in the long term in patients with metastatic castration-resistant prostate cancer (CRPC) who received radiotherapy following progression on docetaxel.
Major finding: The OS significantly improved with ipilimumab vs placebo at 5-12 months (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.51-0.86) and beyond 12 months, (HR, 0.66; 95% CI, 0.52-0.84). OS rates were significantly higher with ipilimumab vs placebo at 2 years (25.2% vs 16.6%) and 5 years (7.9% vs 2.7%). Ipilimumab vs placebo was associated with a higher rate of Grade ≥3 adverse events (76% vs 52%).
Study details: Final analysis of the phase 3 CA184-043 trial in which 799 patients with metastatic CRPC were randomly assigned to receive radiotherapy to bone metastases, followed by either ipilimumab (n = 399) or placebo (n = 400).
Disclosures: The study was funded by Bristol-Myers Squibb (BMS). MB McHenry and A Chen are employees of BMS. The remaining authors reported ties with various pharmaceutical companies, including BMS.
“Immune checkpoint blockade has become a standard part of treatment for many advanced solid tumors. However, this has not been the case in prostate cancer, with some exceptions. There is some evidence that radiation may be beneficial to patients with oligometastatic disease and that radiation may enhance immunotherapy efficacy. Fizazi et al report updated overall survival results from a phase 3 trial where patients previously treated with docetaxel were treated with radiation and randomized to ipilimumab versus placebo. In the initial report, there was no difference in the median overall survival between the 2 groups. The authors now report year-by-year overall survival for years 1 through 5 post-treatment and demonstrate higher overall survival in the group receiving ipilimumab at post-treatment years 2, 3, 4, and 5. While the evidence does not support use of ipilimumab in this setting, it is hypothesis-generating.”
Mark Klein, MD
Fizazi K et al. Eur Urol. 2020 Aug 15. doi: 10.1016/j.eururo.2020.07.032.