Abstract 2628
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.
Legal entity responsible for the study
Janssen Research and Development.
Funding
Janssen Research and Development.
Editorial Acknowledgement
Editorial assistance for this poster was provided by Ann C Sherwood, PhD, and editorial assistance was funded by 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.