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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."

Although the study is small, nonrandomized, and has a brief follow-up, the results are encouraging because of the high rate of BCR after prostatectomy, said AUA expert Adam Weiner, MD, of the University of California Los Angeles.

"It's clear that in many cases this is a disease that requires a multimodal approach with more than one line of therapy upfront to maximize the chance for cure," Weiner told MedPage Today via email. "Radiation with ADT and abiraterone [Zytiga] is clearly supported by level 1 evidence. Prostatectomy with early salvage radiation, if needed, is clearly an option for many patients. We don't have a neoadjuvant or adjuvant systemic therapy option to optimize recurrence rates for patients who are great surgical candidates."

The results are interesting but not unprecedented, said David Y.T. Chen, MD, of Fox Chase Cancer Center in Philadelphia.

"The absence of a control group is a significant limitation of the study and conclusions, and so it is nowhere close to consideration as a new standard of care without a randomized control study getting done," Chen said in an email. "A second but meaningful criticism, the inclusion criteria identifying the eligibility is inadequately defined -- the presented study applies a preoperative set of parameters to determine eligibility, and it more appropriately should be based on postoperative data and pathologic stage, which has greater prognostic accuracy."

Lastly, he continued, "the metric of assessing for recurrence (PSA recurrence) at 24 months after surgery may be of questionable clinical utility, since additional treatment may be very effective and alter a future outcome (such as rate of developing metastasis or death from prostate cancer). To have a change in standard of care regarding prostate cancer would best be following a change that improved overall survival, not simply BCR and PSA recurrence."

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 or .

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 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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