Prostate cancer drug combination adds toxicity without clear benefit for tumors lacking targetable mutations

In a multicenter, randomized phase 2 clinical trial led by the Vall d Hebron Institute of Oncology's Prostate Cancer Group, researchers evaluated the combination of androgen receptor pathway inhibitor enzalutamide and poly(ADP-ribose) polymerase inhibitor talazoparib against enzalutamide alone in patients with high-tumor-burden metastatic prostate cancer who had not previously received hormone therapy.

The results, published in Nature Medicine, showed that the combination treatment extended median radiographic progression-free survival by 14.2 months compared to enzalutamide monotherapy, but did not provide a clear additional clinical benefit in patients without actionable mutations and was associated with increased toxicity. The study, which included 54 patients, also investigated tumor adaptation to resistance to hormonal therapy, known as castration resistance, by integrating longitudinal tumor biopsies with spatially resolved transcriptomic analyses within a randomized clinical trial framework.