New findings were presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium ( ASCO GU ) in San Francisco, and were simultaneously published in The New England Journal of Medicine, from the phase 3 SPARTAN clinical trial that showed treatment with Apalutamide ( Erleada ), an investigational, next-generation androgen receptor inhibitor, decreased risk of metastasis or death by 72% and improved median metastasis-free survival ( MFS ) by more than two years ( difference of 24.3 months ) in patients with non-metastatic castration-resistant prostate cancer ( CRPC ) whose prostate specific antigen ( PSA ) is rapidly rising, compared to placebo.
SPARTAN, a phase 3, randomized, double-blind, placebo-controlled, multicenter study, enrolled 1,207 patients with non-metastatic castration-resistant prostate cancer and was conducted at 332 sites in 26 countries in North America, Europe, Asia-Pacific and Australia. Patients were randomized 2:1 to receive Apalutamide in combination with androgen deprivation therapy ( ADT ) ( n=806 ), or placebo in combination with ADT ( n=401 ).
Apalutamide in combination with ADT decreased the risk of metastasis or death by 72% compared to placebo in combination with ADT ( hazard ratio, HR = 0.28; 95% CI, 0.23-0.35; P less than 0.0001 ).
The median MFS was 40.5 months for Apalutamide in combination with ADT compared to 16.2 months for placebo in combination with ADT, prolonging MFS by more than two years.
MFS benefit was consistently seen across all subgroups of patients.
In addition to improving metastasis free survival, Apalutamide in combination with ADT, compared to placebo in combination with ADT, has demonstrated clinical improvement across secondary endpoints, with statistically significant improvements in time to metastasis ( TTM; median of 40.5 months in the Apalutamide arm compared to median of 16.6 months in the placebo arm ) and progression-free survival ( PFS; median of 40.5 months in the Apalutamide arm compared to median of 14.7 months in the placebo arm ).
Treatment with Apalutamide decreased the risk of symptomatic progression by 55% compared with placebo ( HR=0.45; 95% CI, 0.32-0.63; P less than 0.0001 ).
Apalutamide was associated with a 30 percent risk reduction of death compared to placebo at this early interim analysis for overall survival ( OS ).
In exploratory endpoints, Apalutamide in combination with ADT, compared to placebo in combination with ADT, also achieved a 94% risk reduction in time to PSA progression ( HR = 0.06; 95% CI, 0.05-0.08; P less than 0.0001 ), and a 51% risk reduction in second progression-free survival ( PFS2 ).
The combination of Apalutamide and ADT was tolerable, with maintenance of overall health-related quality of life.
The most common grade 3/4 treatment-emergent adverse events ( TEAEs ) for Apalutamide in combination with ADT versus placebo in combination with ADT were rash ( 5.2% vs. 0.3% ), fall ( 1.7% vs. 0.8% ) and fracture ( 2.7% vs. 0.8% ).
Treatment discontinuation due to adverse events were 11% in the Apalutamide arm compared to 7% in the placebo arm.
Rates of serious adverse events ( SAEs ) were similar in the Apalutamide in combination with ADT arm versus placebo in combination with ADT arm ( 25% vs. 23%, respectively ).
Apalutamide is an oral androgen receptor ( AR ) inhibitor that blocks the androgen signaling pathway in prostate cancer cells.
Apalutamide inhibits the growth of cancer cells in three ways: by preventing the binding of androgen to the AR; by stopping the AR from entering the cancer cells; and by preventing the AR from binding to the DNA of the cancer cell.
Non-metastatic castration-resistant prostate cancer refers to a disease stage when the cancer no longer responds to medical or surgical treatments that lower testosterone, but has not yet been discovered in other parts of the body using a total body bone scan or CT scan.
Features include: lack of detectable metastatic disease; rapidly rising prostate-specific antigen while on androgen deprivation therapy and serum testosterone level below 50 ng/dL.
Ninety percent of patients with non-metastatic CRPC will eventually develop bone metastases, which can lead to pain, fractures and spinal cord compression.
The relative 5-year survival rate for patients with distant stage prostate cancer is 30%. ( Xagena )
Source: Janssen, 2018