Apalutamide (Erleada) and enzalutamide (Xtandi) are oral medications used in the treatment of prostate cancer. They belong to a class known as androgen receptor inhibitors, which target the pathways that drive prostate cancer growth. This article aims to compare these two treatments, providing an overview of their mechanisms, approved uses, clinical outcomes, side effects, and factors considered when choosing between them.
How Apalutamide and Enzalutamide Work
Prostate cancer cell growth is frequently stimulated by male hormones called androgens. Both apalutamide and enzalutamide function by blocking the androgen receptor, a protein within prostate cancer cells that androgens bind to. This binding normally triggers processes that lead to cancer cell proliferation. These drugs are considered next-generation androgen receptor pathway inhibitors. By inhibiting the androgen receptor, they prevent the hormones from stimulating the cancer cells. This action disrupts the signaling cascade that promotes tumor growth, thereby slowing the progression of prostate cancer.
Approved Medical Uses
Apalutamide and enzalutamide have specific approvals for different stages of prostate cancer, with some overlap in their indications. Apalutamide (Erleada) received its initial FDA approval in February 2018 for non-metastatic castration-resistant prostate cancer (nmCRPC), where the cancer is resistant to hormone therapy but has not yet spread. Subsequently, in September 2019, apalutamide was also approved for metastatic castration-sensitive prostate cancer (mCSPC, indicating its use when the cancer has spread but still responds to hormone therapy.
Enzalutamide (Xtandi) has a broader range of approvals. It began with metastatic castration-resistant prostate cancer (mCRPC) in August 2012 for patients who had previously received chemotherapy. In 2014, its approval was expanded to include chemotherapy-naïve mCRPC. Similar to apalutamide, enzalutamide was approved for nmCRPC in 2018 and mCSPC in December 2019. Most recently, in November 2023, enzalutamide gained approval for non-metastatic castration-sensitive prostate cancer with biochemical recurrence at high risk for metastasis.
Key Differences in Clinical Outcomes and Side Effects
Clinical trials have demonstrated that both apalutamide and enzalutamide significantly improve progression-free survival and overall survival in their approved patient populations. A real-world analysis in patients with metastatic castration-sensitive prostate cancer (mCSPC) indicated that apalutamide provided a 23% reduction in the risk of death at 24 months compared to enzalutamide, with 87.6% of apalutamide-treated patients alive versus 73.9% for enzalutamide. While this suggests a potential survival benefit for apalutamide in mCSPC, direct head-to-head randomized trials are not available.
Both medications are oral and typically taken once daily, but their side effect profiles differ. Both drugs can also cause significant drug interactions by inducing CYP3A4, CYP2C9, and CYP2C19 enzymes, which can affect the levels of other medications like warfarin or direct oral anticoagulants.
Common side effects for apalutamide include fatigue, skin rash, joint pain, high blood pressure, and an increased risk of falls and fractures. Serious skin reactions, such as Stevens-Johnson syndrome, can occur.
Enzalutamide’s common side effects include fatigue, hot flashes, high blood pressure, musculoskeletal pain, and headache. A notable distinction is the potential for seizures with enzalutamide, which occurred in 0.5% of patients in clinical trials, with a higher rate of 2.2% in patients with predisposing factors for seizures.
Choosing the Right Treatment
The decision between apalutamide and enzalutamide is individualized, considering a patient’s overall health and disease characteristics.
A healthcare provider evaluates factors such as age, existing medical conditions, the specific stage of prostate cancer, patient tolerance to potential side effects, and current medications for drug interactions.
Ultimately, the choice involves a thorough discussion between the patient and their healthcare provider, weighing the benefits and risks to determine the most appropriate treatment option for their unique situation.