Adding abiraterone acetate plus prednisone (AAP) to androgen deprivation therapy (ADT) significantly increases the magnitude and depth of PSA responses in patients with high-risk metastatic castration-sensitive prostate cancer (mCSPC), and this correlates strongly with improved radiographic progression-free and overall survival, investigators concluded.
The finding is from a post hoc analysis of the LATITUDE study, a randomized, double-blind trial that included 1199 patients with high-risk mCSPC: 597 who received AAP-ADT and 602 who received placebo plus ADT.
At 6 months, 40% of patients in the combined-treatment arm achieved a PSA level of 0.1 ng/mL or less compared with 6.5% in the placebo arm, Nobuaki Matsubara, MD, of the National Cancer Center Hospital East in Chiba, Japan, and colleagues reported in European Urology. Among patients treated with AAP-ADT, those who achieved a PSA level of 0.1 ng/mL or lower in 6 months or less had significant 51%, 56%, and 78% decreased risks of radiographic progression, death, and PSA progression, respectively, compared with PSA nonresponders (those with less than a 50% decline in PSA from baseline). Patients who achieved a PSA level of 0.1 ng/mL or lower in 12 months or less had significant 76%, 74%, and 84% decreases risks of those outcomes, respectively.
In the AAP-ADT group, PSA50 responders (those with a confirmed 50% decrease in PSA from baseline values) had a significant 56% decreased risk of death and 74% decreased risk of radiographic progression compared with nonresponders, according to the investigators.
The median nadir PSA level was 0.09 ng/mL in the AAP-ADT group compared with 2.36 ng/mL in the ADT-placebo group. The time to PSA nadir (TPN) was significantly longer in the AAP-ADT group (6.44 vs 3.07 months).
Median time to PSA progression was significantly longer in the AAP-ADT than ADT-placebo group (33.2 vs 7.4 months). Longer TPN correlated with longer median time to radiographic progression. Among patients with a TPN of 12 or more months, 6 to 12 months, and less than 6 months, the median time to radiographic progression was 40.4, 26.8, and 13.9 months, respectively. The median time to death was 29.6 months among patients with a TPN less than 6 months, but not estimable among patients with a TPN of 12 or more months and 6 to 12 months.
Matsubara N, Chi KN, Özgüroğlu M, et al. Correlation of prostate-specific antigen kinetics with overall survival and radiological progression-free survival in metastatic castration-sensitive prostate cancer treated with abiraterone acetate plus prednisone or placebos added to androgen deprivation therapy: Post hoc analysis of phase 3 LATITUDE study [published online December 13, 2019]. Eur Urol. 2019