Real-world study: Better outcomes with earlier use of enzalutamide in Chinese mCRPC patients
Chinese patients with metastatic castration-resistant prostate cancer (mCRPC) have higher response rates, longer survival and a lower risk of fatigue when enzalutamide is used in earlier rather than later lines of treatment, a study by the Hong Kong Society of Uro-Oncology has shown.
The study included 117 patients with mCRPC treated with enzalutamide at all public oncology centres in Hong Kong between August 2015 and October 2017. Among these patients, 29.1 percent received enzalutamide as first-line therapy, 48.7 percent received enzalutamide as second-line therapy (after docetaxel or abiraterone), and 19.3 percent received enzalutamide at third line or above (after at least two of the following: docetaxel, abiraterone, cabazitaxel or radium-223). [ASCO GU 2018, abstract 330]
After a median follow-up of 7.8 months, median overall survival (OS) was not reached in patients who received enzalutamide as first-line therapy, 15.8 months in those who received enzalutamide as second-line therapy, and 7.4 months in those who received the agent at third line or above (p=0.0002). One-year OS rate was 82 percent.
Median progression-free survival (PFS) was 7.1 months, 3.9 months and 2.2 months in patients who received enzalutamide at first, second and third line or above, respectively (p=0.0002).
Similarly, rates of prostate-specific antigen (PSA) response (>50 percent decline in PSA from baseline) were also higher in patients treated with enzalutamide earlier in the course of their disease. PSA response rate was 73.5 percent in patients treated with first-line enzalutamide, 35.1 percent in patients who received enzalutamide as second-line therapy (post-docetaxel, 53.8 percent; post-abiraterone, 29.5 percent), and 19.2 percent in those who received enzalutamide at third line or above (p<0.001).
“The presence of PSA response was associated with favourable OS [hazard ratio (HR), 0.19; p<0.0001] and PFS [HR, 0.29; p<0.001] in multivariate analysis of the whole cohort,” said first author Dr Darren Poon of the Department of Clinical Oncology, Chinese University of Hong Kong.
The researchers also assessed fatigue in the cohort as real-world data on fatigue in enzalutamide-treated mCRPC patients were lacking. Overall, 54.7 percent and 9.4 percent of patients experienced grade 1/2 and grade 3/4 fatigue, respectively.
Grade 1/2 fatigue was experienced by 44.1 percent of patients treated with first-line enzalutamide, 59.6 percent of patients who received enzalutamide as second-line therapy (post-docetaxel, 47.1 percent; post-abiraterone, 59.1 percent), and 57.7 percent of patients who received enzalutamide at third line or above. The rate of grade 3/4 fatigue was 5.9 percent, 7 percent (post-docetaxel, 0 percent; post-abiraterone, 9.1 percent), and 19.2 percent, respectively.
“In multivariate analysis of the whole cohort, the use of enzalutamide at third line or above was significantly associated with grade 2 or above fatigue [HR, 8.05; p=0.01],” the investigators reported.
“In a real-world clinical setting, more frequent PSA response, longer OS and longer PFS were found in chemotherapy-naïve patients with mCRPC treated with enzalutamide. Patients who received enzalutamide at later lines of treatment had higher risk of fatigue,” they concluded.