Which is better, enzalutamide/enzalutamide or abiraterone?

In the systemic treatment of prostate cancer, enzalutamide and abiraterone are the two most widely used new endocrine therapy drugs in clinical practice. Both are used to treat castration-resistant prostate cancer (CRPC) and metastatic castration-sensitive prostate cancer (mHSPC), but there are significant differences in their mechanisms of action, drug metabolism, usage, side effect profiles, and individualized efficacy. Therefore, there is no absolute standard for "which one is better". The key lies in the patient's specific illness, physical condition and treatment goals.

Enzalutamide is a selective androgen receptor inhibitor that targets the downstream stages of androgen signaling. It not only blocks the binding of androgens to their receptors, but also prevents the receptors from translocating into the nucleus and binding toDNA, thereby comprehensively inhibiting the response of cancer cells to androgen stimulation. The advantage of enzalutamide is that it does not depend on the synthesis level of androgens in the adrenal glands or testicles, and is suitable for use in prostate cancer patients with different hormonal backgrounds, especially in patients who are unwilling to accept or are not suitable for the use of corticosteroids.

The mechanism of Abiraterone focuses on the source of androgen synthesis. It blocks the synthesis of androgens in the adrenal gland, testis and prostate tumor tissue by inhibiting theCYP17 enzyme, so it has a significant effect in reducing androgen levels in the body. However, precisely because it acts on the steroid synthesis pathway, it must be combined with glucocorticoids such as prednisone to avoid adverse reactions caused by up-regulation of mineral corticosteroids, such as water and sodium retention, hypertension, hypokalemia, etc. Although the combination of hormones can improve the efficacy, long-term use of corticosteroids may bring hidden burdens on glucose metabolism and the immune system, which is not ideal for patients with potential metabolic syndrome or osteoporosis.

From the perspective of drug metabolism, enzalutamide is mainly metabolized by the liver and has little impact on renal function. It is suitable for patients with mild to moderate renal insufficiency. Abiraterone has higher requirements on liver function, so it needs to be used with special caution in patients with liver damage. In addition, enzalutamide may be more likely to cause central nervous system-related adverse reactions, such as fatigue, decreased concentration, and risk of epilepsy (although rare), while abiraterone is more closely associated with electrolyte imbalance and increased blood pressure.

In terms of clinical strategy, abiraterone is often used in patients who tolerate glucocorticoids well, especially in cases with high endocrine load. Enzalutamide is increasingly used in elderly patients who are not suitable for long-term hormone supplementation or people with other endocrine diseases. At the same time, some studies indicate that in some patients, the two drugs have similar efficacy, but individual differences in drug response may determine the final choice.

It is worth noting that some patients who develop drug resistance after receiving a certain drug may still be sensitive to another drug, which suggests that the two are not completely equivalent substitutes, but can complement each other in the long-term management of prostate cancer. In addition, the roles of the two drugs in specific combination treatment regimens are also constantly expanding, such as collaborative research with chemotherapy drugs or immunotherapy, further improving their flexibility in disease control.

To sum up, enzalutamide and abiraterone have their own characteristics and both occupy an important position in the clinical path of treating prostate cancer. “Which one is better” cannot be generalized, but requires individualized decision-making based on factors such as the patient’s age, comorbidities, previous medications, treatment response, and quality of life expectations.

Reference materials:https://www.xtandi.com/