Abstract 626P
Background
In the LATITUDE study, abiraterone acetate plus prednisone (AAP) added to androgen deprivation therapy demonstrated significant overall survival (OS) benefit in patients with high-risk metastatic castration-sensitive prostate cancer (mCSPC), compared with placebo (PBO). Around 60% of patients received life-extending subsequent therapies (LEST) after PBO discontinuation. To our knowledge, this is the first analysis to estimate the real treatment effect adjusting for patients without LEST.
Methods
We conducted a post-hoc analysis of data from the LATITUDE study, applying intention-to-treat (ITT) analysis and a naïve-censoring and inverse probability of censoring weighting (IPCW) methods to the PBO group to reveal the proportion of LEST in patients with PBO. In a naïve-censoring approach, patients who did not receive LEST were censored at the date of protocol treatment discontinuation. The IPCW method in this study could represent conditions in which all patients had switched to LEST, unless they died possibly related to protocol treatment, adjusted by baseline and time-varying covariates. The OS hazard ratio (HR) of AAP versus PBO and associated 95% confidence interval (CI) were estimated using a Cox proportional hazards model.
Results
Of 581 patients in the PBO group eligible for LEST, 344 (59.2%) patients received LEST. OS results per the ITT analysis, naïve-censoring method, and IPCW method are shown in the table. The naïve-censoring method and IPCW method provided smaller but significantly better treatment effect estimate than the ITT estimate. Table: 626P
| Method | Median OS, months (95%CI) | HR (95%CI) | |
| AAP (n=597) | PBO (n=602) | ||
| ITT analysis | 53.3 (48.2-not estimable) | 36.5 (33.5-40.0) | 0.66 (0.56-0.78) |
| Naïve-censoring method | Same as ITT analysis | 40.5 (36.5-46.8) | 0.74 (0.63-0.88) |
| IPCW method | Same as ITT analysis | 38.9 (35.4-44.7) | 0.73 (0.61-0.86) |
Conclusions
Treatment with AAP continued to demonstrate significant and clinically meaningful survival benefit over PBO in patients with high-risk mCSPC, regardless of receiving LEST in the PBO group.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Janssen Pharmaceutical K.K.
Disclosure
N. Matsubara: Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Research Grant: Janssen; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Chugai; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Ono; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Pfizer. Y. Koroki: Financial Interests, Personal, Full or part-time Employment: Janssen Pharmaceutical K.K. K. Fizazi: Financial Interests, Institutional, Advisory Board: Amgen; Financial Interests, Institutional, Advisory Board: Astellas; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Advisory Board: AAA; Financial Interests, Institutional, Advisory Board: Bayer; Financial Interests, Institutional, Advisory Board: Clovis; Financial Interests, Institutional, Advisory Board: Curevac; Financial Interests, Institutional, Advisory Board: ESSA; Financial Interests, Institutional, Advisory Board: Genentech; Financial Interests, Institutional, Advisory Board: Janssen; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Advisory Board: Orion; Financial Interests, Institutional, Advisory Board: Sanofi. All other authors have declared no conflicts of interest.