In February 2018, the Food and Drug Administration (FDA) approved apalutamide (trade name: Erleada), a new drug for prostate cancer, for those whose tumors have not metastasized (non metastatic), but whose tumors continue to grow after endocrine therapy (depression-resistant).
This is the first drug approved by the FDA for non-metastatic resistant prostate cancer.
Desmotherapy, which is generally achieved by surgical removal of the testicle (surgical desmothering) or the use of drugs to suppress testosterone production (pharmacologic desmothering), is the standard of care for patients with metastatic or nonmetastatic prostate cancer. Unfortunately, denervation eventually fails in almost all patients, leading to what is known as “denervation-resistant prostate cancer.
In patients who have not yet developed metastases, a rapid increase in prostate-specific antigen (PSA) levels means that metastases will soon occur, putting the patient at increased risk of death. Previously, there was no good treatment for this group of patients.
We know that androgens (such as testosterone) promote prostate tumor growth, and apalutamide, a new generation of competitive androgen receptor inhibitors, prevents androgens from binding to androgen receptors, thereby inhibiting tumor growth.
Apalutamide was approved primarily based on a randomized, double-blind, placebo-controlled, phase 3 clinical trial called SPARTAN. This clinical trial was conducted in 26 countries in North America, Europe, and Asia Pacific.
SPARTAN study
SPARTAN study: Apalutamide delays prostate cancer metastasis by 2 years
This phase 3 clinical trial included more than 1,200 patients with non-metastatic debulking-resistant prostate cancer. Patients were randomized to two groups, treated with apalutamide (240 mg daily) or placebo. All patients had received endocrine therapy, such as a luteinizing hormone releasing hormone ( leuteinizing hormone releasing hormone, LHRH) agonist or antagonist, or orchiectomy.
Results showed that apalutamide reduced the risk of distant tumor metastasis or death by 72%. Metastasis-free survival, the primary indicator of efficacy, was 40.5 months in the apalutamide group compared with 16.2 months in the placebo group, an increase of more than two years. This means that apalutamide delayed the time to tumor metastasis by two years in patients with non-metastatic debulking-resistant prostate cancer!
For safety, the main adverse reactions associated with apalutamide treatment included fatigue, hypertension, rash, diarrhea, nausea, weight loss, joint pain, falls, hot flashes, decreased appetite, fractures, and swelling of the extremities. Among them, serious adverse reactions mainly include falls, fractures and convulsions.
Apalutamide has been included in the NCCN guidelines
Based on these findings, the 2018 update of the National Comprehensive Cancer Network (NCCN) guidelines has included apalutamide as a treatment for non-metastatic destructive resistant prostate cancer (Non-metastatic castration resistant prostate cancer (M0 CRPC) patients as second-line therapy.
For non-metastatic destructive resistant prostate cancer, the NCCN guidelines recommend “continued use of an LHRH agonist or antagonist to maintain destructive serum testosterone levels (<50 ng/dL) in combination with the second-generation anti-androgen drug apalutamide. “.
At present, apalutamide is not yet available in China, but relevant clinical trials have been conducted in China, and interested patients can ask their doctors for information about clinical trials.