Apalutamide Extends Metastasis-Free Survival In High-Risk Prostate Cancer

SPARTAN study findings support the use of the androgen receptor blocker apalutamide in castration-resistant prostate cancer patients at risk of developing metastases

medwireNews: For men with high-risk castration-resistant prostate cancer, a phase III study shows that the first development of metastatic disease can be slowed by combining the androgen receptor (AR) inhibitor apalutamide with androgen deprivation therapy (ADT).

The results from the SPARTAN trial were presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco, California, USA, and simultaneously published in The New England Journal of Medicine.

The primary endpoint of radiologically measured metastasis-free survival was a median of 40.5 months for the 806 men with a prostate-specific antigen (PSA) doubling time of 10 months or less who were randomly assigned to receive apalutamide 240 mg/day plus ADT.

This was significantly higher than the median of 16.2 months achieved by the 401 patients who were treated with placebo plus ADT, giving a hazard ratio (HR) for metastasis or death of 0.28.

Indeed, apalutamide was associated with improved median metastasis-free survival when considering age, race, geographical region, baseline PSA level and doubling time, nodal status, number of prior hormone therapies and use of bone-sparing agents, and ECOG performance status.

On entry into the trial, the patients underwent bone scans and computed tomography of the pelvis, abdomen, chest and head. “It is possible that more sensitive imaging tests could have identified metastases at baseline in many of the patients in our trial, particularly because of the requirement for a short PSA doubling time at trial entry”, observe Matthew Smith, from Massachusetts General Hospital Cancer Center in Boston, USA, and co-authors.

“The consistent increase in metastasis-free survival associated with apalutamide across all patient subgroups […], however, suggests that the clinical benefits of apalutamide extend to patients with a high disease burden”, they write.

Apalutamide plus ADT also resulted in significantly longer median values for the prespecified secondary endpoints of progression-free survival (40.5 vs 14.7 months, HR 0.29) and time to symptomatic progression (unreached in both groups, HR 0.45).

And there were trends towards improved outcomes with apalutamide for the secondary endpoints of longer median overall survival and time to initiation of cytotoxic chemotherapy, as well as the exploratory endpoint of time to second progression-free survival, all of which the researchers believe “support the clinical benefit of apalutamide.”

Grade 3 or 4 adverse events occurred in 45.1% of the apalutamide arm and 34.2% of controls, with serious events reported for 24.8% and 23.1%, respectively, the authors report.

Nevertheless, progressive disease was the most common reason for discontinuation in the apalutamide and control arms, affecting 19.3% and 52.8% of patients, respectively, while adverse events led to discontinuation in a corresponding 10.6% and 7.0%.

Specifically, the researchers attribute the higher rates of fatigue (30.4 vs 21.1%), rash (23.8 vs 5.5%), falls (15.6 vs 9.0%), fracture (11.7 vs 6.5%), hypothyroidism (8.1 vs 2.0%) and seizure (0.2 vs 0.0%) among the apalutamide-treated patients to the AR inhibitor use.

“The benefits of apalutamide treatment for men with nonmetastatic castration-resistant prostate cancer should be weighed against the potential harms”, Matthew Smith et al conclude.

Reference

Smith MR, Saad F, Chowdhury S, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med; Advance online publication 8 February 2018 . DOI: 10.1056/NEJMoa1715546

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