In an analysis reported in the Journal of Clinical Oncology, Verheijden et al found that higher peak corticosteroid doses for patients with immune-related adverse events were associated with poorer outcomes in patients receiving immune checkpoint inhibitors (ICIs) for solid tumors.
Study Details
The study involved data from 1,959 patients receiving combined anti–PD-1 and anti–CTLA-4 treatment in six international phase II/III European Medicines Agency registrational trials: CheckMate trials 067 (for advanced melanoma, n = 313), 142 (for microsatellite instability–high or mismatch repair–deficient colorectal cancer, n = 119), 214 (for advanced renal cell carcinoma, n = 547), 648 (for advanced esophageal squamous cell carcinoma, n = 322), 743 (for malignant pleural mesothelioma, n = 300), and 9LA (for metastatic non–small cell lung cancer, n = 358).
Key Findings
Among the 1,959 patients in the study population, 834 were treated with immunosuppression for immune-related adverse events. A total of 832 received corticosteroids, and 81 received second-line immunosuppressants.
High corticosteroid peak dose was associated with worse progression-free survival, with adjusted hazard ratios of 1.15 (95% confidence interval [CI] = 1.02–1.29) for 1 mg/kg vs 0.5 mg/kg prednisolone-equivalent and 1.43 (95% CI = 1.05–1.96) for 2 mg/kg vs 0.5 mg/kg prednisolone-equivalent. Similar effects were observed for overall survival, with adjusted hazard ratios of 1.21 (95% CI = 1.06–1.39) for 1 mg/kg vs 0.5 mg/kg and 1.66 (95% CI = 1.17–2.37) for 2 mg/kg vs 0.5 mg/kg.
Higher cumulative corticosteroid dose was not significantly associated with outcomes; each 1,000-mg increase was associated with adjusted hazard ratios of 0.98 (95% CI = 0.93–1.03) for progression-free survival and 0.96 (95% CI = 0.91–1.01) for overall survival.
No apparent associations were found between second-line immunosuppressant use vs no use and progression-free survival (adjusted hazard ratio [HR] = 1.23, 95% CI = 0.90–1.68) or overall survival (adjusted HR = 1.25, 95% CI = 0.88–1.77).
The investigators concluded: “Higher corticosteroid peak dose for immune-related adverse events is associated with worse survival across tumor types, while cumulative dose is not. Too few patients received second-line immunosuppressants to confirm or reject an association with survival. These data argue for a reconsideration of immune-related adverse event management approaches, starting with lower corticosteroid dose whenever feasible.”
Karijn P.M. Suijkerbuijk, MD, PhD, of the Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, the Netherlands, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
