Incidence and relative risk of adverse events of special interest in patients with castration resistant prostate cancer treated with CYP-17 inhibitors: A meta-analysis of published trials

⿢Toxicities including fluid retention/edema, hypokalemia, hypertension, liver function test abnormalities and cardiac events were more frequent during CYP-17 inhibitor based therapy.⿢CYP-17 inhibitors significantly increase the risk all grades: hypertension, hypokalemia, cardiac disorders and liver function test abnormalities.⿢CYP-17 inhibitors significantly increase the risk of grade ⿥ 3 events: hypokalemia and cardiac disorders.

Abiraterone acetate and orteronel are two CYP-17 inhibitors that have been studied in prostate cancer. They have shown relevant toxicities, including fluid retention/oedema, hypokalaemia, hypertension, liver function test abnormalities and cardiac events. The goal of this study was to determine the risk of special adverse events related to CYP- 17 inhibitor in patients with metastatic castration-resistant prostate cancer (CRCP). Summary data from four randomized phase III trials comparing CYP-17 inhibitors and prednisone versus placebo and prednisone in metastatic CRCP patients were meta-analysed. Pooled risk ratios (RRs) for the risk of all-grade and grade 3⿿4 adverse events of special interest were calculated. Data from 4916 patients (2849 in the AA experimental arm; 2067 in the control arm) were analysed. The incidence of grade 3⿿4 adverse events was never more than 10% of the patients. However, compared with placebo, the CYP-17 inhibitor significantly increased the all-grade events of hypertension (RR = 1.53; 95% CI = 1.3⿿1.8; p < 0.00001), hypokalaemia (RR = 1.56; 95% CI = 1.29⿿1.89; p < 0.00001), cardiac disorders (RR = 1.47; 95% CI = 1.27⿿1.7; p < 0.00001) liver function test abnormalities (RR = 1.93; 95% CI = 1.15⿿3.24; p = 0.01) grade ⿥ 3 adverse events, hypokalaemia (RR = 4.23; 95% CI = 1.28⿿13.99; p = 0.02) and cardiac disorders (RR = 1.55; 95% CI = 1.18⿿2.05; p = 0.002). A lot of adverse events such as hypertension, hypokalaemia, cardiac disorders and liver function test abnormalities are increased during CYP-17 inhibitor based therapy. Strict monitoring of these side effects should be considered during CYP- 17 inhibitor therapy in prostate cancer patients.