Abstract
Novel oral anti-androgens (NOAAs) represent a new class of drugs that are being approved for prostate cancer. However, fatigue and anemia are among the most common treatment-related symptoms. Hence, we conducted a meta-analysis of randomized controlled trials (RCTs) to investigate the relative risks (RRs) of fatigue and anemia associated with NOAAs. PubMed, Cochrane, EMBASE, and abstracts presented at the annual meeting of the American Society of Clinical Oncology and European Society of Clinical Oncology were searched for phase III and V RCTs of NOAAs from January 2000 to March 2020. Safety profile from each selected study was evaluated for all-grade and high-grade fatigue and anemia adverse events. The RRs with 95% confidence intervals (95% CIs) were calculated using random-effects for all-grade and high-grade events.Our analysis involved 15 RCTs, including 16,795 patients. Overall, 9,177 patients were treated with NOAAs in the experimental arm, whereas 7,095 received a standard of care in the control arm. The RR of all-grade and high-grade fatigue was 1.26 (95% CI 1.15-1.38) and 1.24 (95% CI 0.83-1.84), and that of all-grade and high-grade anemia was 0.81 (95% CI 0.77-1.19) and 0.81 (95% CI 0.61-1.06), respectively. Our findings suggest that NOAAs are associated with an increased risk of fatigue but decreased risk of anemia. Patients should be frequently monitored to identify adverse events to improve oncological outcomes and optimize the overall treatment efficacy and safety. Not all the RCTs addressed fatigue and anemia simultaneously as side effects of NOAA treatment.
Highlights
BackgroundProstate cancer (PC) is the second most common malignancy in men and the fifth leading cause of cancerrelated death in men worldwide
Novel oral anti-androgens (NOAAs): novel oral anti-androgen; SOC: standard of care; non-metastatic castrate-resistant PC (nmCRPC): non-metastatic castrate-resistant prostate cancer; metastatic hormone-sensitive PC (mHSPC): metastatic hormone-sensitive prostate cancer; metastatic castrate-resistant PC (mCRPC): metastatic castrate-resistant prostate cancer nmCRPC had the highest risk of high-grade fatigue (85%; relative risks (RRs) 1.85, 95% confidence intervals (95% CIs) 0.38-9.14, I2= 71%), followed by mHSPC (55%; RR 1.55, 95% CI 0.73-3.29, I2= 71%), and mCRPC (14%; RR 0.86, 95% CI 0.66-1.12, I2= 0%, Figure 9)
NOAA: novel oral anti-androgen; SOC: standard of care; nmCRPC: non-metastatic castrate-resistant prostate cancer; mHSPC: metastatic hormone-sensitive prostate cancer; mCRPC: metastatic castrate-resistant prostate cancer nmCRPC had the highest risk of all-grade anemia (23%; RR 1.23, 95% CI 0.77-1.96, I2= 0%), followed by mHSPC (8%; RR 0.92, 95% CI 0.65-1.30, I2= 88%), and mCRPC (12%; RR 0.88, 95% CI 0.73-1.07, I2= 0%, Figure 10)
Summary
BackgroundProstate cancer (PC) is the second most common malignancy in men and the fifth leading cause of cancerrelated death in men worldwide. The first generation of these drugs, including bicalutamide, nilutamide, and flutamide [5] that were used as therapy for the management of advanced PC since 1941 [6], did not fully block androgen receptor activity. The US Food and Drug Administration has permitted four novel oral anti-androgens (NOAAs): abiraterone acetate, enzalutamide, and recently, apalutamide and darolutamide [7,8]. These agents prevent testicular and extragonadal testosterone synthesis either by inhibiting the key enzyme in androgen production, cytochrome P450 17A1, as abiraterone acetate does, or by inhibiting the nuclear translocation of androgen receptors in the prostate, as enzalutamide, darolutamide, and apalutamide do [7]
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