(UroToday.com) The 2023 American Urological Association (AUA) annual meeting held in Chicago, IL between April 28 and May 1st, 2023, was host to an invasive bladder cancer podium session. Dr. Daniele Robesti presented the results of a pooled analysis of individual participant data from IMvigor210 and IMvigor211 evaluating the immune-related adverse events paradox in locally advanced or metastatic urothelial cancer patients receiving atezolizumab.
Immune checkpoint inhibitors (ICI) are increasingly utilized for the treatment of patients with urothelial carcinoma. However, the relationship between immune-related AEs and patient outcomes remains poorly understood. The objective of this study was to investigate the association between immune-related AEs and oncologic outcomes in patients with advanced urothelial carcinoma receiving ICIs. To this end, the investigators performed a combined analysis of individual participant data from two prospective trials, IMvigor210 and IMvigor211, evaluating atezolizumab in patients with advanced urothelial carcinoma.
This analysis included a total of 896 patients. Patients were split into one of two cohorts: those who experienced an immune-related AE and those who did not. Baseline characteristics were balanced across both groups, with the exception of a lower proportion of visceral metastases (68% versus 78%) and higher proportion of PD-L1 positive expression in the group experiencing immune-related AEs.
The Kaplan-Meier curves below (blue: immune-related AE, red: no immune-related AE) demonstrated superior PFS and OS outcomes in the group that experienced immune-related AEs.
PFS
These findings were confirmed on multivariable analyses, with occurrence of immune-related AEs associated with superior:
- OS: HR 0.51, 95% CI 0.41 – 0.64
- CSS: HR 0.55, 95% CI 0.45 – 0.72
- PFS: HR 0.50, 95% CI 0.40 – 0.61
Dr. Robesti acknowledged the potential for an immortal time bias in this cohort of patients, whereby those in the immune-related AE group had to survive until such an event occurred. As such, in the time between start of ICI and occurrence of immune-related AEs, no adverse oncologic outcomes could have occurred.
To address this potential issue, sensitivity analysis adjusting the “T0” to 68 days, which was the median time to occurrence of an immune-related AE, demonstrated consistent superior OS and PFS outcomes in the immune-related AE cohort.
Based on these results, Dr. Robesti concluded that the development of immune-related AEs secondary to atezolizumab immunotherapy for locally-advanced or metastatic urothelial cancer is associated with improved oncologic outcomes.
Presented by: Daniele Robesti, MD, Urology Resident Physician, Università Vita-Salute San Raffaele, Milan, Italy
Written by: Rashid K. Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 American Urological Association (AUA) Annual Meeting, Chicago, IL, April 27 – May 1, 2023