Apalutamide (Erleada) demonstrates a statistically significant and clinically meaningful improvement in overall survival (OS) compared to enzalutamide (Xtandi) in patients with metastatic castration-sensitive prostate cancer (mCSPC). The findings come from a retrospective analysis presented at the 6th European Conference of Oncology Pharmacy (ECOP). The study highlights a 23% reduction in the risk of death at 24 months for patients treated with apalutamide versus enzalutamide (HR, 0.77; 95% CI, 0.62-0.96; P = .019).
The real-world head-to-head study evaluated 3719 ARPI-naïve patients with mCSPC. Among them, 1810 patients initiated apalutamide, and 1909 initiated enzalutamide. The primary endpoint of the analysis was 24-month OS, with exploratory analysis evaluating OS using all available follow-up. The results remained consistent when evaluating OS using all follow-up (HR, 0.77; 95% CI, 0.64-0.93; P = .008).
Consistency with TITAN Trial
The proportion of patients alive at 24 months in the apalutamide arm of the retrospective study aligns with findings from the phase 3 TITAN trial (NCT02489318). In the TITAN trial, the OS rate in the apalutamide plus androgen-deprivation therapy (ADT) arm was 82.4% at 24 months, compared to 87.6% in the real-world analysis. A final analysis of the TITAN trial reported a 48-month OS rate of 65.1% for patients who initiated treatment with apalutamide.
Expert Commentary
"This real-world evidence showed a statistically significant and clinically meaningful improvement in survival with apalutamide over enzalutamide in patients with mCSPC at 24 months," said Neal Shore, MD, FACS, chair of the Steering Committee and medical director at the Carolina Urologic Research Center. He further noted the importance of this study in the absence of prospective ARPI comparator trials, offering valuable insights for prescribers.
Patient Characteristics and Methodology
The mean patient age in the study was 73 years, with approximately 60% White and 23% Black. Bone, nodal, and visceral metastases were observed in approximately 72%, 49%, and 20% of patients, respectively. Androgen deprivation therapy was used in approximately 81% of patients at the time of index, defined as the first prescription date for either ARPI therapy. Patients were excluded if they had castration-resistant prostate cancer, prior ARPI use, advanced treatment, or an additional primary cancer.
Implications for Treatment
Luca Dezzani, MD, United States vice president of Medical Affairs at Johnson & Johnson Innovative Medicine, emphasized that apalutamide is the only ARPI to demonstrate a survival benefit as early as 22 months, as seen in the TITAN study. He highlighted the significance of this evidence in showing an OS benefit with apalutamide, which is administered as a single, once-daily pill.
