Apalutamide efficacious in previously treated patients

September 10, 2019

Researchers say the use of apalutamide (Erleada) in patients with high-risk, nonmetastatic castration-resistant prostate cancer improves metastasis-free survival in patients who have previously undergone radical prostatectomy or external radiotherapy-regardless of the type of treatment they received.

Researchers say the use of apalutamide (Erleada) in patients with high-risk, nonmetastatic castration-resistant prostate cancer improves metastasis-free survival (MFS) in patients who have previously undergone radical prostatectomy or external radiotherapy-regardless of the type of treatment they received.

A recent clinical trial showed the use of apalutamide in patients with high-risk nonmetastatic castration-resistant prostate cancer demonstrates a more than 2-year increase in MFS and a 55% reduction in time to symptomatic progression (N Engl J Med 2018; 378:1408-18).

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In the current study, presented at the AUA annual meeting in Chicago, researchers sought to determine whether treatment with apalutamide, a next-generation androgen receptor inhibitor, provided the same benefit and safety profile in patients who had previously undergone radical prostatectomy and/or external radiotherapy as it does in those who have not.

The authors, from multiple institutions, separated patients randomly into two groups: those who received apalutamide (240 mg once per day) and androgen deprivation therapy (ADT) and those who received a placebo and ADT. The apalutamide-plus-ADT group was about twice as large as the ADT-and-placebo group. Forty-one percent of patients in each group (334/806 apalutamide; 166/401 placebo) had undergone radical prostatectomy or external radiotherapy prior to the study. Patient outcomes were evaluated based on any radical prostatectomy or external radiotherapy received prior to the study.

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Regardless of the type of local therapy patients with high-risk, nonmetastatic castrate-resistant prostate cancer previously received-radical prostatectomy or external radiotherapy-use of apalutamide significantly increased MFS compared with similar patients who were given a placebo. This result held true across all subgroups of patients who had undergone prior treatment and were taking apalutamide.

Placebo patients who had previously undergone radical prostatectomy or external radiotherapy demonstrated worse MFS compared with patients who had not previously received these treatments.

Median time from initial diagnosis to randomization was 3.7 years (apalutamide) and 2.2 years (placebo), respectively, in patients who had previously undergone radical prostatectomy and/or external radiotherapy and those who had not. Further study is needed to determine whether a longer time to randomization among these patients was associated with the presence of more aggressive disease when treatment was initiated.

“At the beginning of the study, we thought men who had undergone prior therapy would have better outcomes,” first author Boris A. Hadaschik, MD, chair of urology at University Hospital Essen in Essen, Germany, told Urology Times. These men were younger; recorded lower PSA values, ECOG, and Gleason scores; were less likely to have renal impairment; and had experienced a longer time since diagnosis compared with others in the study. However, the results showed that despite these advantages, patients who had previously undergone radical prostatectomy or external radiotherapy had poorer outcomes. MFS was significantly shorter for placebo patients who had prior local therapy than those who had not.

This is one area where treatment with apalutamide made a significant difference. Use of apalutamide in patients with prior local therapy delayed development of metastases by 68% to 84% compared with similar patients who received a placebo.

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Additionally, the relative magnitude of improvement with apalutamide versus use of a placebo was highest among patients who had previously undergone radical prostatectomy and/or had been treated with external radiotherapy.

Meanwhile, incidence of falls, fractures, hypothyroidism, seizures, and skin rash was similar in patients with or without radical prostatectomy or external radiotherapy.

The use of prior therapy did not impact patients’ tolerability for apalutamide, the authors found.

“MFS on conventional imaging is a bit of an artificial endpoint for prostate cancer trials. All patients are still being followed for overall survival, and updated results of the SPARTAN study will be presented at ESMO,” Dr. Hadaschik told Urology Times.

The FDA’s approval of apalutamide for treatment of nonmetastatic castration-resistant prostate cancer represents the first use of MFS as a primary endpoint to support drug approval. Apalutamide is also the first drug approved to treat nonmetastatic castration-resistant prostate cancer.

Janssen Research & Development provided funding for the study.

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