LATITUDE study: PSA response characteristics and correlation with overall survival (OS) and radiological progression-free survival (rPFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) receiving ADT+abiraterone acetate and prednisone (AAP) or placebo (PBO)
2018-10-01

Background: The randomized, double-blind, active-controlled LATITUDE study found that AAP + ADT significantly improved the primary end points, OS and rPFS vs ADT+PBO in patients with high risk mHSPC. Post hoc analyses were performed to assess correlation of PSA response with OS and rPFS. Methods: 597 men received ADT+AAP and 602 received ADT+PBO. PSA response (confirmed) was based on PCWG2 criteria. Hazard ratios (HR) between treatment arms were determined using Cox proportional-hazards model. Kendall's tau was used to evaluate correlations. Results: The overall median (med) baseline PSA was 23.85 ng/mL (range 0.0; 8889.6). Addition of AAP to ADT improved all PSA parameters. Patients receiving AAP were significantly more likely to achieve 50% PSA response (Relative Risk (RR): 1.36) and 90% PSA response (RR: 2.30) vs PBO. Compared to nonresponders, the 50% and 90% PSA response to AAP reduced the risk of death by ≈56% and ≈89% (HR: 0.435 and 0.107, respectively), and by ≈41% and ≈72% (HR: 0.590 and 0.283 respectively) with PBO. A similar effect was noted on rPFS. Further, ADT+AAP demonstrated increasing potential of attaining PSA <0.2 ng/mL at 3, 6 and 12 months (RR: 5.15, 6.35, 6.33, respectively). In the ADT+AAP group, 58% patients reached PSA <0.2 vs 12.8% with PBO. The med time to PSA nadir was 6.4 mo and 3.8 mo in the ADT+AAP and the ADT+PBO groups, respectively. The significantly prolonged med time to PSA nadir in the ADT+AAP group (HR:0.644) was accompanied by a markedly deeper med nadir PSA value (AAP:0.09 ng/mL [range 0.02; 1269.79] vs PBO:2.36 ng/mL [range 0.02; 2254.50]). Lastly, AAP significantly delayed med time to PSA progression as compared to PBO (33.2 mo vs 7.4 mo, respectively; HR: 0.3, p < 0.0001) and the time to PSA progression strongly correlated with rPFS (Kendall's tau = 0.9211) and OS (Kendall's tau = 0.666). Conclusions: Treatment of high-risk mHSPC with ADT+AAP demonstrates a significant depth of PSA response that strongly correlates with long-term outcomes of rPFS and OS. Clinical trial identification: NCT01715285. Editorial acknowledgement: Editorial assistance for this poster was provided by Ann C Sherwood, PhD, and editorial assistance was funded by Janssen Research and Development. Legal entity responsible for the study: Janssen Research and Development. Funding: Janssen Research and Development. Disclosure: K.N. Chi: Institutional funding: Janssen for the study; Grant funding: Astellas, Bayer, Sanofi Janssen; Personal fees: Astellas, Bayer, Sanofi, Essa, Roche. M. Ozguroglu: Honoraria: Janssen, Sanofi. A. Rodriguez Antolin: Consulting services, Expert testimony: Astellas, Bayer, Janssen. S. Feyerabend: Advisory boards: Janssen, Boehringer Ingelheim Pharma, Aventis, Honorarium: Janssen, Travel and accommodation expenses: Aventis. L. Fein: Grant support, Personal fees: Novartis, Pfizer, Roche, Merck, Merck Sharp & Dohme; Grant support: Janssen, AbbVie. B.Y. Alekseev: Personal fees: Janssen, Pfizer, Merck, Roche, Sanofi. A. Protheroe: Consulting, Advisory roles, Travel, accommodations, and expenses: Ipsen, Bayer, Roche, Bristol-Myers Squibb, Merck; Research funding: Merck. G. Sulur, S. Li, P. De Porre, N. Tran, S.D. Mundle: Employee, Stock Owner: Janssen Research & Development. K. Fazazi: Advisory boards; Honoraria: Janssen, Astellas, Sanofi, and Bayer. All other authors have declared no conflicts of interest.