No PSA Recurrence at 24 Months With Apalutamide Plus ADT After Radical Prostatectomy

SAN ANTONIO — More than 2 years after treatment, no patient with high-risk prostate cancer had a confirmed biochemical recurrence after receiving postoperative apalutamide (Erleada) and androgen deprivation therapy (ADT), according to a single-arm, phase II study.

Two unconfirmed recurrences occurred at 24 and 30 months. Including those cases resulted in a 24-month biochemical recurrence-free survival (BCRFS) of 98.4%, increasing to a perfect 100% when only confirmed cases were considered, reported Jason Hafron, MD, of the Michigan Institute for Urology in Bloomfield, Michigan, at the American Urological Association annual meeting.

“You rarely ever see a flat Kaplan-Meier curve,” said Hafron. “Again, no patient had a confirmed BCR 2 years after radical prostatectomy, defined as two consecutive PSA [prostate specific antigen] values greater than 0.2 nanograms per milliliter.”

“The naysayers in this room would say ‘Of course you’re going to have an undetectable PSA. They were on apalutamide and ADT,'” he added. “But please realize that 76% of the patients had a testosterone recovery of greater than or equal to 150 nanograms per deciliter 12 months after completing treatment, and 95% of the patients at 12 months had testosterone levels greater than or equal to 50 nanograms per deciliter.”

About 15% of newly diagnosed prostate cancers meet criteria for high risk, and 45-65% of those cancers recur within 5 years after radical prostatectomy, Hafron noted in his introduction. The selective androgen receptor inhibitor apalutamide is being evaluated in two registrational trials of high-risk localized prostate cancer treated with prostatectomy or radiation therapy.

Hafron reported findings from the trial of postoperative apalutamide plus ADT in men undergoing radical prostatectomy for high-risk localized prostate cancer (defined as PSA ≥20 ng/mL or one of several high-risk Gleason grades). A retrospective study of 3,500 men with high-risk prostate cancer showed a 2-year BCRFS of 76% with radical prostatectomy alone. Those results provided the reference for the current study.

Data analysis included 96 patients enrolled at 27 sites in the U.S. They had a postoperative PSA ≤0.2 ng/mL and no evidence of metastatic disease. All patients received 12 cycles of apalutamide plus ADT. The primary endpoint was BCRFS at 24 months. Secondary endpoints included BCRFS at 12 months and serum testosterone recovery to ≥150 ng/dL at 18 and 24 months. Unconfirmed BCR was an exploratory endpoint.

Gleason score at diagnosis was 8 in 30% of patients and 9 in 57%. The cohort had a median preoperative PSA of 7.6 ng/mL and median testosterone of 340 ng/dL. Consistent with FDA guidance regarding clinical trial diversity, 14% of patients were Black/African American.

The results showed no confirmed PSA recurrences during the first 24 months after treatment. The two unconfirmed events occurred at 24 and 30 months, associated with PSA values of 0.39 and 0.22 ng/mL, respectively.

With respect to testosterone recovery, 35% of patients had recovery to ≥150 ng/dL within 6 months, and 63% had recovery to ≥50 ng/dL, in addition to the 12-month rates of 76.4% and 95.2%.

The most common treatment-emergent adverse events (TEAEs) were hot flush (68.5%), fatigue (53.7%), rash (21.3%), COVID-19 (17.6%), and arthralgia (16.7%). The most common grade 3 TEAEs (no grade 4) were fatigue (3.7%), rash (2.8%), and COVID-19 (1.9%). TEAEs leading to discontinuation occurred in 10.2% of the study population.

“Treatment intensification with 12 cycles of apalutamide and ADT could become an option for patients with high-risk localized prostate cancer who have undergone radical prostatectomy,” said Hafron.

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