Abstract 651P
Background
Visceral metastases (VM), largely in lungs and liver, are uncommon in men with advanced prostate cancer. This subgroup analysis of the phase 3 LATITUDE study (NCT01715285) assessed the impact of AAP on overall survival (OS) and radiographic progression-free survival (rPFS) in men with mCSPC and VM.
Methods
Men with newly diagnosed mCSPC enrolled in the LATITUDE study were randomized (1:1) to AAP + androgen deprivation therapy (ADT) or placebo + ADT (PBO). Patients with VM in liver or lungs with or without other soft tissue and bone metastases (based on CT/MRI) at baseline were included in this subgroup analysis. Coprimary efficacy endpoints, OS and rPFS were assessed using the Kaplan-Meier method. Non-stratified Cox regression model was used to estimate hazard ratios (HR) and 95% CI.
Results
Among 1199 patients who received either AAP + ADT or PBO + ADT, 228 (19%) had VM at baseline (114 in each group), of which 53 (AAP: 29, PBO: 24) had liver metastases and 117 (AAP: 60, PBO: 57) had lung metastases. AAP showed comparable improvement vs PBO in OS in patients with VM (median 55.4 vs 33.0 months; HR: 0.582; 95% CI: 0.406-0.835; p=0.0029). Improvement in rPFS was also observed following AAP treatment vs PBO in patients with VM (median 30.7 vs 18.3 months; HR: 0.527; 95% CI: 0.366-0.759; p=0.0005). The incidence of treatment-emergent adverse events was similar between patients with VM (112 [98.2%]) and without VM (103 [90.4%]). Table: 651P
| Lung (but not liver) metastases (n=117) | Liver metastases (n=53) | |||
| AAP (n=60) | PBO (n=57) | AAP (n=29) | PBO (n=24) | |
| OS (months) | 57.2 | 37.9 | 36.8 | 25.6 |
| HR (95% CI) | 0.60 (0.35, 1.04) | 0.82 (0.41, 1.66) | ||
| rPFS (months) | 33.0 | 21.9 | 10.9 | 14.6 |
| HR (95% CI) | 0.50 (0.29, 0.89) | 1.05 (0.53, 2.09) |
Conclusions
AAP improved both rPFS and OS in men with mCSPC and visceral disease, especially those with lung metastases. Presence of liver metastases was associated with a poorer prognosis than lung metastases. Whether patients with de novo liver metastases benefit or not from next generation androgen receptor targeting requires additional data.
Clinical trial identification
NCT01715285.
Editorial acknowledgement
Editorial assistance was provided by Ramji Narayanan of SIRO Clinpharm Pvt Ltd and funded by Janssen Global Services, LLC.
Legal entity responsible for the study
Janssen Research & Development, LLC.
Funding
Janssen Research & Development, LLC.
Disclosure
G. Baciarello: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Amgen; Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas Oncology; Travel/Accommodation/Expenses: Ipsen. S.D. Mundle: Full/Part-time employment: Janssen. G. Leitz: Full/Part-time employment: Janssen. U. Richarz: Full/Part-time employment: Janssen. P. Hu: Full/Part-time employment: Janssen. K.N. Chi: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Astellas Pharma; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Bayer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Janssen; Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Sanofi; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: ESSA; Research grant/Funding (institution): Lilly/ImClone; Research grant/Funding (institution): Merck ; Advisory/Consultancy, Research grant/Funding (institution): Roche; Research grant/Funding (institution): Tokai Pharmaceuticals ; Research grant/Funding (institution): Bristol-Myers Squibb. K. Fizazi: Honoraria (self), Advisory/Consultancy: Astellas Pharma; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy: Sanofi; Advisory/Consultancy, Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: Curevac; Advisory/Consultancy: ESSA; Advisory/Consultancy: Orion Pharma GmbH; Advisory/Consultancy: Roche; Advisory/Consultancy: Genentech. All other authors have declared no conflicts of interest.