Posted: Monday, October 17, 2022
An article published in Clinical Cancer Research presented findings from a phase Ib study examining the safety and efficacy of GS-5829, an oral BET inhibitor, alone and in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer. Rahul Aggarwal, MD, of the University of San Francisco Helen Diller Family Comprehensive Cancer Center, and colleagues examined BET because it is known to regulate proteins in patients with this type of prostate cancer and to exhibit antitumor activity. The researchers’ findings revealed that although the BET inhibitor was generally tolerated, it showed limited efficacy and high interpatient variability.
The study comprised 31 men with confirmed metastatic castration-resistant prostate cancer. GS-5829 was administered in a sequential dose escalation orally once daily, at 0.6, 1.4, 2, 3, 4, 6, 9, and 12 mg. The primary endpoint was non–disease progression rate at week 24; secondary endpoints included prostate-specific antigen level reduction from baseline, progression-free survival, and pharmacokinetics and safety of GS-5829.
Overall findings revealed that all patients had at least one treatment-emergent adverse event. A total of 11 patients (52.4%) had a grade 3 or higher event, and 12 (57.1%) experienced at least one adverse event related to GS-5829. Overall, no adverse events leading to death were reported. The estimated median rate of progression-free survival was 2.79 months (95% confidence interval = 2.60 months–3.29 months). Since all but two patients discontinued the study for causes other than death, the overall survival rate was not evaluable. Additional findings revealed there were no dose-dependent increases in pharmacokinetic parameters, but there was a high degree of interpatient variability across all doses tested.
“Although the clinical development of GS-5829 has been terminated based on these findings, the attractiveness of the target warrants exploration of other BET inhibitors in castration-resistant prostate cancer and other cancers,” the study authors concluded.
Disclosure: For full disclosures of the study authors, visit aacrjournals.org.