Biomarkers Pinpoint Resistant Prostate Cancer That May Benefit From Addition of Apalutamide

By Marilynn Larkin

June 17, 2021

NEW YORK (Reuters Health) - Biomarkers can be used to identify patients with prostate cancer refractory to first-line androgen deprivation therapy (ADT) who might benefit from the addition of apalutamide to standard treatments, researchers say.

"Patients with a high Decipher (genomic test) score clearly benefit the most from the addition of apalutamide to standard treatments," Dr. Felix Feng of the University of California San Francisco told Reuters Health by email.

"Moreover," he said, "patients with the basal subtype of prostate cancer should be selected for further intensification of therapy beyond apalutamide, in clinical trials."

Because blood tests, such as PSA levels, can be used to monitor treatment response, prostate cancer patients do not undergo regular biopsies when the disease recurs, he said. "One of the most surprising findings from our study was that a patient's initial biopsy sample can provide valuable information on how that patient will respond to treatment many years later."

The average time between initial biopsy and enrollment in the SPARTAN trial, samples from which were analyzed for the current study, was close to seven years, he noted. "It is remarkable that biomarkers from a tumor sample can predict a patient's response to apalutamide seven years later!"

Dr. Feng and colleagues analyzed gene expression data from 233 archived samples from patients (median age, 75) with nonmetastatic castration-resistant prostate cancer (nmCRPC) enrolled in the SPARTAN trial for their study, published in JAMA Oncology.

Patients had been randomized (2:1) to 240mg/d apalutamide plus ADT (apalutamide+ADT) or placebo+ADT. The team stratified the patients as at high-risk or low-risk for developing metastases based on genomic classifier (GC) scores for high (GC >0.6) and low to average (GC up to 0.6), and into basal and luminal subtype. Half had high GC scores.

All patients receiving apalutamide+ADT had improved outcomes. However, high GC scores were associated with the greatest improvement in metastasis-free survival (MFS; hazard ratio, 0.21); overall survival (OS; HR, 0.52), and time to second progression (PFS2; HR, 0.39) compared to placebo+ADT.

Sixty-five percent of patients had the basal molecular subtype. In the placebo+ADT arm, no significant differences were seen in MFS, PFS2, or OS between patients with the luminal versus basal subtype. However, in the apalutamide+ADT arm, patients with the luminal subtype had a significantly longer MFS (HR, 0.40) compared with basal subtype HR, 0.66).

Similar trends were observed for OS (HR, 0.50 for apalutamide+ADT vs. HR, 0.78 for placebo+ADT) and PFS2 (0.71 vs. 0.72).

In regression analysis, the luminal-basal subtype score was significantly associated with MFS in patients receiving apalutamide+ADT (HR, 2.65); by contrast, GC score was significantly associated with MFS in placebo+ADT recipients (HR, 2.09).

Dr. Feng added, "Based on our study, I believe that biomarkers like basal subtyping should be used to select which patients should be enrolled in clinical trials looking at adding more intensive treatments to apalutamide, for patients with aggressive disease."

Dr. Luke Pike of Memorial Sloan Kettering Cancer Center on New York City, coauthor of a related editorial, commented in an email to Reuters Health, "I think the key take-away from this study is that genomic/transcriptomic tests such as Decipher will likely play an important role in treatment selection and prognosis in a variety of settings in the future."

"Right now," he said, "Decipher is mainly used to determine whether or not an otherwise low risk, localized prostate cancer patient harbors more aggressive disease, which could make a patient an unsuitable candidate for active surveillance."

"However," he added, "this study shows that we'll likely see the use of tests like this in more advanced settings and aggressive disease."

"As discussed in the editorial, I would not suggest that providers use Decipher for decision making for CRPC on the basis of this study," he said. "While compelling, the study was underpowered to show statistical interaction, and furthermore, it is a retrospective analysis of prospectively collected samples, so it's not strictly appropriate to use such data in making clinical recommendations."

"However," he concluded, "the future looks bright for the use of 'omics' in prostate cancer!"

The study was funded by Janssen Research and Development LLC. Four coauthors are employees and Dr. Feng and several coauthors have received fees from the company.

SOURCE: https://bit.ly/35s8o3t and https://bit.ly/3vwiXNI JAMA Oncology, online June 3, 2021.

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