SAN FRANCISCO—Ipilimumab added to radiation therapy (RT) increased median overall survival (OS) in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) and specific prognostic features compared with RT alone, according results of prespecified subset analyses reported at the 2014 Genitourinary Cancers Symposium.
Previously, the phase 3 CA184-043 study (NCT00861614) did not reach statistical significance for its primary endpoint, OS (hazard ratio [HR], 0.85; P = 0.053). However, based on antitumor activity observed in other efficacy endpoints, such as progression-free survival, subset analyses were performed to determine if any prognostic features could identify patients more likely to benefit from treatment with ipilimumab, noted Charles G. Drake, MD, PhD, assistant professor, oncology, immunology, and urology at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, and colleagues.
In the study, 799 patients with mCRPC were randomly assigned to receive a single dose of RT followed by either ipilimumab (n = 399) or placebo (n = 400). The subset analyses, performed using known prognostic factors for OS in mCRPC, found that having no visceral disease, an alkaline phosphatase level less than 1.5 times the upper limit of normal (ULN), and hemoglobin 11 g/dL or higher all favored treatment with ipilimumab.
For those without visceral metastases, median OS was 14.4 months in the ipilimumab plus RT arm versus 10.3 months for the RT-alone arm (HR, 0.73; 95% CI: 0.59-0.89); with visceral metastases, median OS was 5.7 versus 7.4 months, respectively (HR, 1.2; 95% CI: 0.90-1.60). For patients with alkaline phosphatase less than 1.5 times the ULN, median OS was 16.5 months in the ipilimumab plus RT arm versus 12.8 months in the RT-alone arm (HR, 0.78; 95% CI: 0.62-0.97). For those with a hemoglobin 11 g/dL or higher, median OS was 15.3 months in the ipilimumab plus RT arm compared with 12.0 months for the RT-alone arm (HR, 0.79; 95% CI: 0.64-0.97); for a hemoglobin lower than 11 g/dL, this was 5.9 versus 6.9 months, respectively.
Patients also had a longer median OS if they were younger (vs. older) than 70 years of age, had an Eastern Cooperative Oncology Group performance status of 0 (vs. 1), and had a lactate dehydrogenase level greater than or equal to twice the ULN.
Dr. Drake concluded that these results support continued investigation of ipilimumab in the ongoing study in patients with mCRPC who previously have received docetaxel. The estimated study completion date is February 2017.
The 2014 Genitourinary Cancers Symposium is sponsored by the the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO), and the Society of Urologic Oncology (SUO).