KEY TAKEAWAYS
- The phase 3 IMvigor010 trial aimed to analyze the irAEs correlation with ctDNA using a modified Cox model.
- The analyses suggested higher low-grade irAE risk in ctDNA-negative patients on atezolizumab, supporting increased treatment-related toxicity, aligning with trials like IMvigor011.
Results from the IMvigor010 trial revealed a roughly 40% reduction in the risk of death with atezolizumab in post-cystectomy ctDNA-positive patients. The potential of ctDNA to forecast immune checkpoint inhibition toxicity still remains unclear. The absence of tumor-induced immune suppression may contribute to an increase in immune-related adverse events (irAEs).
For the study, researchers studied 300 high-risk muscle-invasive bladder cancer patients treated with atezolizumab, and 281 were observed post-surgical resection with baseline ctDNA assessment.
Cox regression, adjusted for various factors, analyzed the association between baseline ctDNA and time to onset of the first specific immune-related adverse event (irAE) in the atezolizumab arm. Cumulative incidence function plots visualized irAE risk over time, considering death as a competing event in safety endpoints analysis.
In patients with high-risk muscle-invasive bladder cancer, the risk of low-grade irAEs was notably higher in ctDNA-negative individuals compared to ctDNA-positive ones at baseline (ctDNA-negative vs. -positive: HR 1.97 [1.29, 2.99]).
Patients with lower baseline ctDNA levels had an increased risk (ctDNA log-MTM/mL: HR 0.92 [0.87, 0.97]). Low-grade irAEs, primarily hepatitis, hypo-/hyperthyroidism, and rash, were observed.
There was no clear association between baseline ctDNA and high-grade irAEs due to limited event numbers. Analysis of on-treatment ctDNA-irAE was inconclusive due to restricted safety data availability.
The exploratory analysis revealed a heightened risk of low-grade irAEs in ctDNA-negative compared to ctDNA-positive patients receiving adjuvant atezolizumab. It aligned with the hypothesis of elevated treatment-related toxicity in patients without cancer.
The findings corroborate insights from other ctDNA trials, including IMvigor011.
Source: https://jitc.bmj.com/content/11/Suppl_1/A494
Clinical Trial: https://clinicaltrials.gov/study/NCT02450331
Carter C, Madjar K, Balas BI, et al445 The relationship between immune-related adverse events (irAEs) and ctDNA status: exploratory analysis from IMvigor010Journal for ImmunoTherapy of Cancer 2023;11:doi: 10.1136/jitc-2023-SITC2023.0445.
