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
2881 - Impact of corticosteroids and antibiotics on efficacy of immune-checkpoint inhibitors in advanced non-small cell lung cancer
Presenter: Joaquin Mosquera Martinez
Session: Poster Display session 3
Resources:
Abstract
3186 - The landscape of immuno-oncology clinical trials in China
Presenter: Dawei Wu
Session: Poster Display session 3
Resources:
Abstract
3468 - Clinical Significance of Immune-related Creatine Phosphokinase Increase Associated with Anti PD1/PD-L1 immunotherapies.
Presenter: Samia Hajem
Session: Poster Display session 3
Resources:
Abstract
3836 - Thyroid toxicity and anti-thyroid antibodies as predictive markers for patients treated with anti-PD1 checkpoint therapy
Presenter: Wim Meer
Session: Poster Display session 3
Resources:
Abstract
1343 - Treatment-related adverse events and tolerability in patients with advanced renal cell carcinoma treated with first-line combination therapy with checkpoint inhibitors
Presenter: Thura Win Htut
Session: Poster Display session 3
Resources:
Abstract
5783 - Immune-related adverse events (irAEs) with single-agent PD-1 vs PD-L1 inhibitors: a meta-analysis of 8,730 patients from clinical trials
Presenter: Guru Sonpavde
Session: Poster Display session 3
Resources:
Abstract
5422 - EULAR recommendations for the diagnosis and the management of rheumatic immune-related adverse events due to cancer immunotherapy
Presenter: Marie Kostine
Session: Poster Display session 3
Resources:
Abstract
1202 - Radiographic characteristics and poor prognostic factors of interstitial lung disease (ILD) in nivolumab-treated patients with non-small cell lung cancer (NSCLC)
Presenter: Shinichi Sasaki
Session: Poster Display session 3
Resources:
Abstract
2749 - Use of Checkpoint Inhibitors (CPI) in Allogeneic Stem Cell Transplant Recipients: An Institutional Experience and A Systemic Review of the Literature
Presenter: Chantal Saberian
Session: Poster Display session 3
Resources:
Abstract
3256 - Deep Learning Radiomics distinguishes intrapulmonary Disease from Metastases in Immunotherapy-treated Melanoma Patients
Presenter: Thi Dan Linh Nguyen-Kim
Session: Poster Display session 3
Resources:
Abstract