A RECENT clinical trial from the Karolinska Institute, Solna, Sweden, has evaluated and personalised treatments for metastatic castration-resistant prostate cancer (mCRPC), representing a major advancement in treatment options for the disease.
The study, which utilised a biomarker-driven approach to evaluate the effectiveness of androgen receptor pathway inhibitors (ARPI’s) compared to taxane-based chemotherapy, is the first to apply a Bayesian framework in prostate cancer. By analysing circulating tumour DNA and germline DNA, the trial identified biomarker-defined patient groups, including those with specific genetic mutations that might influence their response to treatments. Patients in the study were randomised to receive ARPI’s, taxane chemotherapy, or a physician’s choice of treatment, with the option to be re-randomised if they reached the point of no longer clinically benefitting (NLCB) from their current therapy.
The study’s results demonstrated that ARPIs offer significant advantages over chemotherapy. In a total of 218 randomisations, patients treated with ARPIs showed a 50% longer median time to NLCB compared to those receiving taxanes (11.1 vs. 6.9 months), as well as an improvement in overall survival (38.7 vs. 21.7 months). These findings highlight the potential of ARPIs as a superior first-line treatment for many patients with mCRPC, particularly those with specific genetic profiles, such as androgen receptor (AR)-negative, TP53 wild-type, and TMPRSS2–ERG fusion-positive cases.
However, the study also revealed that not all patients benefit equally from ARPIs, for example, those with TP53-altered tumours did not experience a significant difference in outcomes between ARPIs and chemotherapy, suggesting the need for alternative treatments for this subgroup.
The study’s approach highlights the power of precision oncology, using real-time genetic data to tailor treatments to individual patients. By offering insights into which treatments work best for specific genetic profiles, the study could pave the way for more personalised and effective strategies in prostate cancer care.
Katie Wright, EMJ
Reference
De Laere B et al. Androgen receptor pathway inhibitors and taxanes in metastatic prostate cancer: an outcome-adaptive randomized platform trial. Nat Med. 2024; DOI:10.1038/s41591-024-03204-2. Erratum in: Nat Med. DOI:10.1038/s41591-024-03268-0.
