Abstract 261MO
Background
The CHART trial showcased the survival advantage of rezvilutamide plus androgen deprivation therapy (ADT) over bicalutamide plus ADT in high-volume metastatic hormone-sensitive prostate cancer (mHSPC) patients. This post-hoc analysis aims to evaluate the effect of liver and metabolic toxicities on survival outcomes and quality of life (QoL) among high-volume mHSPC patients receiving rezvilutamide.
Methods
In the CHART trial, mHSPC patients were randomly assigned (1:1) to receive ADT plus either rezvilutamide or bicalutamide. Liver toxicity in this post-hoc analysis encompassed elevated γ-glutamyl transferase, aspartate aminotransferase, alanine aminotransferase or blood bilirubin; metabolic toxicity comprised hypertriglyceridemia, hypercholesterolemia and weight gain. The association between toxicities and survival outcomes and QoL was analyzed.
Results
Among patients treated with rezvilutamide plus ADT, the incidence of liver toxicity and metabolic toxicity was 24.6% and 56.7%, respectively (Table). These toxicities were mostly of grade 1 or 2 and resolved or improved without requiring treatment modification. Patients presenting with metabolic toxicity demonstrated extended progression-free survival (PFS) (HR=0.594, 95%CI 0.400, 0.883, P=0.010) and overall survival (OS) (HR=0.594, 95%CI 0.383, 0.922, P=0.020) than those without. However, no difference in survival was discerned between patients with or without liver toxicity. Notably, patients who developed grade 3 metabolic toxicity displayed superior QoL compared to those without. Table: 261MO
Treatment-related adverse events of special interest (n=323)
| Events, n (%) | Any grade | Grade ≥3 |
| Liver toxicity | 79 (24.6%) | 13 (4.0%) |
| γ-glutamyl transferase increased | 20 (6.2%) | 3 (0.9%) |
| Aspartate aminotransferase increased | 65 (20.1%) | 7 (2.2%) |
| Alanine aminotransferase increased | 62 (19.2%) | 7 (2.2%) |
| Abnormal liver function | 3 (0.9%) | 3 (0.9%) |
| Blood bilirubin increased | 4 (1.2%) | 1 (0.3%) |
| Metabolic toxicity | 183 (56.7%) | 31 (9.6%) |
| Hypertriglyceridemia | 90 (27.9%) | 15 (4.6%) |
| Hypercholesterolemia | 61 (18.9%) | 0 |
| Weight gain | 151 (46.7%) | 16 (5.0%) |
Conclusions
To our knowledge, this is the first study to reveal an association between metabolic toxicity and prolonged PFS and OS in mHSPC patients on rezvilutamide plus ADT, leading to an enhanced QoL.
Clinical trial identification
NCT03520478; May 30th, 2018.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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