ARPIs Beneficial in Prostate Cancer

TOPLINE:

In patients with prostate cancer, androgen receptor pathway inhibitors (ARPIs) extended the median time to no longer clinically benefitting (NLCB) to 11.1 months vs the 6.9 months seen with taxanes. Overall survival was also higher for those taking ARPIs than for those taking taxanes, in the randomized controlled trial.

METHODOLOGY:

• Researchers conducted an outcome-adaptive platform trial involving 343 patients with metastatic castration-resistant prostate cancer across Sweden, Belgium, and Norway.
• Participants were randomized to receive androgen receptor pathway inhibitors (ARPIs), taxanes, or a physician’s choice, with rerandomization occurring upon disease progression
• The primary endpoint was the time to no longer clinically benefitting (NLCB), with secondary endpoints including overall survival and serious adverse events.
• Patients were stratified into biomarker subgroups based on genetic alterations in AR, TP53, homologous recombination deficiency genes, and TMPRSS2-ERG fusion.
• Dosages included 1000 mg of abiraterone acetate or 160 mg of enzalutamide daily for ARPIs, and 75 mg of docetaxel or 20-25 mg/m² of cabazitaxel every 3 weeks for taxanes.

TAKEAWAY:

• ARPIs extended the median time to no longer clinically benefitting (NLCB) to 11.1 months compared to 6.9 months for taxanes.
• Overall survival was significantly longer for patients treated with ARPIs, with a median of 38.7 months vs 21.7 months for taxanes.
• The largest increase in time to NLCB was observed in AR-negative and TP53 wild-type patients, and TMPRSS2-ERG fusion-positive patients.
• No significant difference in time to NLCB was observed between ARPIs and taxanes in TP53-altered patients.

IN PRACTICE:

“The initial results demonstrate the superiority of ARPIs for the biomarker-unselected ‘all’ patient population compared to physician’s choice and taxanes in patients with mCRPC and detectable ctDNA. On average, patients treated with ARPIs experienced a 55% and 77% longer time to NLCB and overall survival, respectively. To our knowledge, these are the first randomized data for comparing outcomes of ARPIs vs taxanes in patients with first-line or second-line mCRPC with detectable ctDNA,” the authors wrote.

SOURCE:

The study was led by Bram De Laere and Alessio Crippa, of the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet in Stockholm, Sweden, and others. It was published online on August 20, in Nature Medicine.

LIMITATIONS:

The study’s limitations include the relatively small sample size, which may affect the generalizability of the findings. Additionally, the absence of data on race and ethnicity may impact the applicability of the results to diverse populations. The study’s open-label design could introduce bias in the assessment of the primary endpoint, time to no longer clinically benefitting (NLCB). Finally, the study’s focus on patients with detectable circulating tumor DNA may limit the generalizability of the findings to those with higher disease burden and poorer prognosis.

DISCLOSURES:

De Laere disclosed receiving grants from Janssen-Cilag and AstraZeneca, and Crippa reported having no competing interests. Two authors reported having filed a patent application for a method of identifying and adjusting for systematic variability in DNA abundance measurements, “which is applied in the current study to identify copy number alterations.” Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.