Improved survival rates have been seen in a study of apalutamide in high risk men with non-metastatic castration-resistant prostate cancer.
A phase 3 trial of the androgen receptor inhibitor versus placebo for men with non-metastatic prostate cancer has shown the drug can extend metastasis-free survival by over two years.
The SPARTAN study, published this week in NEJM and presented at the ASCO 2018 Genitourinary Cancers Symposium in San Francisco, randomised 1,207 men across 332 sites and 26 countries.
All men were free of metastases on conventional imaging but at high risk due to PSA doubling times of less than 10 months. Standard androgen-deprivation therapy was continued during the trial.
Follow-up was for a median of 20 months at which time about 23% of the treated group and 48% of controls had either died or had distant metastases.
The study found the median metastasis-free survival was 40.5 months with apalutamide compared to 16.2 months with placebo.
The effect was observed across all patient sub-groups by age, PSA doubling time, and local or regional nodal disease.
The study reported all secondary end points were also improved in treated patients including time to metastasis, progression-free survival and time to symptomatic progression.
An exploratory end point, time to PSA progression, was not reached by the apalutamide group but was 3.7 months in the control group. PSA levels dropped by 90% in the treated group after 12 weeks but rose by 40% in the controls.
Adverse events associated with the treatment included fatigue, rash, hypothyroidism, arthralgia, weight loss, falls and fractures.
As expected, most metastases were in the bone in both groups.
About 80% of controls received subsequent treatment such as abiraterone plus prednisone for metastatic castration-resistant prostate cancer.
“Although subsequent approved treatment was administered at a high rate in the control group, apalutamide was associated with better results than placebo for secondary end points analysed late in the trial, including time to symptomatic progression, time to the initiation of cytotoxic chemotherapy, and overall survival.”
“Apalutamide was also associated with longer second-progression-free survival than placebo.”
The authors said the consistent increase in metastasis-free survival across all sub-groups suggested the clinical benefit of apalutamide would extend to patients with a high disease burden.