Abstract 4574
Background
Three recent RCT (Spartan, Prosper and Aramis) have demonstrated improved metastasis-free survival with new ARi Apalutamide (A), Enzalutamide (E) and Darolutamide (D), respectively, vs placebo (pl) in nmCRPC. We conducted a meta-analysis of RCT to evaluate the safety of ARi.
Methods
Random-effects meta-analysis was performed to describe pooled odds ratio (OR) vs pl and presence of heterogeneity in the effect among RCT. Network meta-analysis was performed to describe OR of indirect comparisons.
Results
4104 patients were included in safety analysis. Many adverse events (AEs) (falls, fractures, fatigue, nausea, diarrhea, hypertension, rash) showed a significant difference in the incidence in patients receiving pl, mostly higher in the Spartan trial. The use of ARi was associated with an higher risk of developing selected AEs compared to pl: serious AEs (OR 1.28, 95%CI 1.10-1.50); falls (OR 1.81, 95%CI 1.40-2.34); fractures (OR 1.58, 95%CI 1.11-2.23); fatigue (all grades OR 2.00, 95%CI 1.68-2.39; severe OR 2.21, 95%CI 1.06-4.60); rash (OR 4.90, 95%CI 3.24-7.41); diarrhea (OR 1.24, 95%CI 1.00-1.54); hypertension (all grades OR 1.55, 95%CI 1.25-1.92; severe OR 1.44, 95%CI 1.08-1.92); dizziness (OR 1.67, 95%CI 1.26-2.21), mental impairment (OR 1.73, 95%CI 1.13-2.66). Significant heterogeneity in the effect among ARi was found for falls (D better than E: OR 0.29, 95%CI 0.14-0-60; D better than A: OR 0.48, 95%CI 0.25-0.91); fatigue all grades (D better than E: OR 0.59, 95%CI 0.39-0.88; A better than E: OR 0.61, 95%CI 0.44-0.84) and severe (D Better than E: OR 0.10, 95%CI 0.02-0.60); hypertension (D better than E: OR 0.51, 95%CI 0.27-0.98; A better than E: OR 0.53, 95%CI 0.31-0.92); mental impairment (D better than E: OR 0.15, 95%CI 0.04-0.58; D better than A: OR 0.24, 95%CI 0.06-0.90). No significant heterogeneity was found for other AEs.
Conclusions
With the limitations of the network meta-analysis, our findings suggest that the use of ARi in nmCRPC is associated with a statistically significant increased risk of developing selected AEs according to the type of agent used. Potential specific toxicities should be considered before starting ARi in nmCRPC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Altavilla: Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Janssen. M. Di Maio: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Merck Sharp & Dohme; Honoraria (self): Roche; Honoraria (self): AstraZeneca; Honoraria (self): Janssen; Honoraria (self): Takeda; Research grant / Funding (institution): Tesaro. M. Tucci: Honoraria (self): Astellas; Honoraria (self): Janssen; Honoraria (self): Bayer; Honoraria (self): Sanofi. U. De Giorgi: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy: Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol Meyer Squibb; Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer. All other authors have declared no conflicts of interest.
Resources from the same session
5877 - Efficacy of anti-PD(L)1 treatment in patients with metastatic urothelial cancer based on mRNA- and protein- based PD-L1 determination: Results from the multicentric, retrospective FOsMIC trial
Presenter: Jonas Jarczyk
Session: Poster Display session 3
Resources:
Abstract
5204 - A differential bladder microbiota composition is associated with tumor grade in bladder cancer.
Presenter: Monica Parra-Grande
Session: Poster Display session 3
Resources:
Abstract
4904 - Molecular characterization of metastatic urothelial carcinoma (mUC) in prior or current smokers (PCS) vs non-smokers (NS)
Presenter: Victor Sacristan Santos
Session: Poster Display session 3
Resources:
Abstract
5370 - Evaluation of different diagnostic methods for identification of FGFR alteration in advanced urothelial carcinomas: Proficiency Results based on multiple RNA extraction kits and mutation detection methods
Presenter: Veronika Weyerer
Session: Poster Display session 3
Resources:
Abstract
2579 - Title: Genomic characterization of non-schistosomiasis-related squamous cell carcinoma (NSR-SCC) of the urinary bladder: a retrospective study of potential prognostic and predictive biomarkers
Presenter: Esmail Al-ezzi
Session: Poster Display session 3
Resources:
Abstract
2203 - TiNivo: Tivozanib combined with nivolumab results in prolonged progression free survival in patients with metastatic renal cell carcinoma (mRCC). Final Results.
Presenter: Philippe Barthelemy
Session: Poster Display session 3
Resources:
Abstract
4712 - First-Line Pembrolizumab (pembro) Monotherapy for Advanced Non‒Clear Cell Renal Cell Carcinoma (nccRCC): Updated Follow-Up for KEYNOTE-427 Cohort B
Presenter: Cristina Suárez
Session: Poster Display session 3
Resources:
Abstract
2091 - First-Line Pembrolizumab (pembro) Monotherapy in Advanced Clear Cell Renal Cell Carcinoma (ccRCC): Updated Follow-Up For KEYNOTE-427 Cohort A
Presenter: James Larkin
Session: Poster Display session 3
Resources:
Abstract
2368 - Association Between Depth of Response and Overall Survival: Exploratory Analysis in Patients With Previously Untreated Advanced Renal Cell Carcinoma (aRCC) in CheckMate 214
Presenter: Viktor Grünwald
Session: Poster Display session 3
Resources:
Abstract
6008 - Quality of life in previously untreated patients with advanced renal cell carcinoma (aRCC) in CheckMate 214: updated results
Presenter: David Cella
Session: Poster Display session 3
Resources:
Abstract