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PSA decline or control was not found to be concordant with PSMA tumor volume changes among enzalutamide-treated patients with BCR prostate cancer.
A lack of concordance was observed between prostate-specific antigen (PSA) decline and/or control and changes in prostate-specific membrane antigen (PSMA) tumor volume following 3 months of enzalutamide (Xtandi) monotherapy for the treatment of patients with biochemically recurrent (BCR) prostate cancer, according to data from a phase 2 study (NCT06096870) presented during the
Findings from the study presented in a poster by Madan revealed that patients who received enzalutamide monotherapy (n = 13) experienced a median PSA response of –98% (range, –88% to –100%) for a duration of 266 days, including 84 days of treatment with the agent. However, the median PSMA tumor volume response was –71.7% (range, 13.2% to –100%). Among patients with a PSA level of 0 ng/mL after enzalutamide (n = 4) the PSMA tumor volume levels were 0 in two patients, –86% in a third patient, and +2.8% in a fourth. Of note, PSMA tumor volume increase in the fourth patient did not predict a poor clinical response and that patient experienced longer PSA control compared with a patient who had a 100% PSA decline and a complete response per PSMA. The median duration of PSA control below baseline was 266 days (range, 210-371).
“These are some of the first data, certainly in [patients with] BCR [prostate cancer], that are looking at PSMA scans after treatment and basically successful PSA responses. These data are from the first 13 patients and are not looking at just any finding on PSA, they are specifically looking at tumor volume,” Madan, a senior clinician in the Genitourinary Malignancies Branch at the National Cancer Institute (NCI) in Bethesda, Maryland, explained in an interview with OncLive®. “These data should be a cautionary tale for trials that are being planned now, because there's a lot of interest in taking PSMA as an intermediate readout to determine if we're going to intensify or de-intensify [treatment], but these data show that that's not really helping us make that determination.”
The phase 2 trial was conducted at the NCI and enrolled adult patients with BCR prostate cancer who previously received either radiation or underwent surgery.2 Patients were required to have an ECOG performance status of less than 2, testosterone levels above 100 ng/dL, and adequate bone marrow and organ function per study protocol. A PSA doubling time within less than 12 months, rising PSA levels, and PSMA-positive disease were also key inclusion criteria.
Patients were randomly assigned to received either enzalutamide at 160 mg once daily on each day of a 28-day cycle or the same dosing regimen of enzalutamide in combination with the subcutaneous interleukin-12 immunocytokine PDS01ADC at 12 μg/kg every 28 days.1,2
“Although the trial is focused on a combination of enzalutamide and the cytokine, it's not fully accrued, so we didn't present any data from the cytokine cohort,” Madan noted.
The primary end point of the study was to determine if enzalutamide plus PDS01ADC was associated with an increase in the duration of PSA suppression compared with enzalutamide. Secondary end points included PET changes after enzalutamide with/without PDS01ADC, safety, immune response, and PSA detection.
At baseline, the first 13 patients in the monotherapy arm had a median age of 71 years (range, 54-79). The median PSA, PSA doubling time, and PSMA tumor volume values were 22.5 ng/mL (range, 3.2-121.5), 3.5 months (range, 2.6-9.1), and 11.1 mL (range, 1.21-45.29), respectively.
“In this current generation, there's a lot of enthusiasm to use PSMA scans to help us understand therapeutic responses, but there's actually very little data to help us understand what that is going to look like,” Madan concluded.
Disclosures: Madan reported receiving research funding from Bayer.
