Corticosteroids for Immune-Related Adverse Events and Checkpoint Inhibitor Efficacy: Analysis of Six Clinical Trials

Author(s): Rik J. Verheijden, MSc^1,2; Jolien S. de Groot, MD, PhD³; Babs O. Fabriek, PhD³; Miki N. Hew, MD, PhD³; Anne M. May, PhD²; Karijn P.M. Suijkerbuijk, MD, PhD¹

Source: https://doi.org/10.1200/JCO.24.00191

Dr. Anjan Patel's Thoughts

Pooled data of nearly 2000 patients across six trials in melanoma using IO therapy. It seems clear that high dose corticosteroid use was associated with worse outcomes, especially with high peak doses. What may be worth considering is if non-steroid based immunosuppression can be used as an adjunct to blunt this concerning effect.

PURPOSE

Retrospective studies suggest that immunosuppressive treatment of immune-related adverse events (irAEs) impairs survival in patients with melanoma who received immune checkpoint inhibitors. Here, we study this association across tumor types using data from six international phase II/III registrational trials.

METHODS

A post hoc analysis was performed on individual patient data from the anti–programmed cell death-1 (anti–PD-1) + anti–cytotoxic T lymphocyte–associated protein-4 (anti–CTLA-4) treatment arms of six clinical trials (CheckMate-067, -142, -214, -648, -743, and -9LA). Among patients who received systemic immunosuppression for treatment-related adverse events (trAEs), associations of peak and cumulative corticosteroid dose, and use of second-line immunosuppression with overall survival (OS) and progression-free survival (PFS) were assessed using multilevel Cox regression with adjustment for age and sex.

RESULTS

Of the 1,959 patients who received anti–PD-1 + anti–CTLA-4 therapy, 834 patients who were treated with immunosuppression for trAEs were included. Eight hundred and thirty-two patients (100%) received corticosteroids and 81 patients (10%) received second-line immunosuppressants. High corticosteroid peak dose was associated with worse PFS: adjusted hazard ratio (HRadj), 1.15 (95% CI, 1.02 to 1.29) for 1 versus 0.5 mg/kg prednisolone and HRadj, 1.43 (95% CI, 1.05 to 1.96) for 2 versus 0.5 mg/kg. Similar effects were observed for OS: HRadj, 1.21 (95% CI, 1.06 to 1.39) and HRadj, 1.66 (95% CI, 1.17 to 2.37) for 1 and 2 versus 0.5 mg/kg, respectively. Cumulative corticosteroid dose was not associated with survival. HRadj of use of second-line immunosuppression was 1.23 (95% CI, 0.90 to 1.68) for PFS and 1.25 (95% CI, 0.88 to 1.77) for OS.

CONCLUSION

Higher corticosteroid peak dose for trAEs 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 irAE management approaches, starting with lower corticosteroid dose whenever feasible.

Author Affiliations

¹Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; ²Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, the Netherlands; ³Medicines Evaluation Board, Utrecht, the Netherlands

Association Between Systemic Anticancer Therapy Administration Near the End of Life With Health Care and Hospice Utilization in Older Adults: A SEER Medicare Analysis of End-of-Life Care Quality

Maybe I’m biased as chair of the VBC, but this study showed that all subtypes of SACT use were associated with markers of poorer-quality EOL care.

Postmastectomy Radiation Therapy: An ASTRO-ASCO-SSO Clinical Practice Guideline

Guidelines for post-mastectomy radiation include patients who received neoadjuvant therapy, with or without residual disease after treatment. A good topic to review.

Novel Systemic Anticancer Treatments and Health Services Use the End of Life Among Adults With Cancer

This study reviewed the effects of using novel agents (immunotherapy and targeted therapy) in patients at the end of life (EOL), based on the perception that these therapies may be less toxic than chemotherapy. Adjusted odds of high health service utilization and hospital death were more than twofold greater among patients receiving systemic anticancer therapy (SACT) at the EOL compared to those receiving none.

Prescribing Changes After Accelerated vs Regular Approval of Oncology Therapies

This study analyzed prescribing patterns for oncology drugs granted FDA Accelerated Approval (AA) versus those later converted to Regular Approval (RA) using data from over 63,000 patients with advanced solid tumors. Prescribing of AA drugs increased sharply—by an average of 23 percentage points—immediately after AA, while conversion to RA led to only a minimal further increase. Off-label use of AA drugs, either in earlier lines of therapy or in biomarker-negative patients, was rare. The findings suggest that oncologists rapidly adopt AA drugs into practice, often without waiting for confirmatory evidence required for RA. In summary, AA status drives substantial and immediate uptake of oncology drugs, highlighting the importance of timely confirmatory trials to ensure clinical benefit.

Mapping the rapid growth of multi-omics in tumor immunotherapy: Bibliometric evidence of technology convergence and paradigm shifts

The article demonstrates that multi-omics research in tumor immunotherapy has grown rapidly since 2019, with China leading in publication volume but showing limited international collaboration. Early research focused on immune checkpoint blockade, while recent trends emphasize machine learning, multi-omics integration, and lncRNA, reflecting a shift toward predictive modeling and biomarker discovery. Multi-omics approaches have enabled the development of immune infiltration-based prognostic models and identified metabolic and spatial biomarkers, such as oxidative phosphorylation in melanoma and ENPP1 in Ewing sarcoma, which may guide therapeutic strategies. Overall, the study provides a systematic framework for tracking technological convergence and emerging frontiers, highlighting the need for longitudinal omics monitoring, AI-driven integration, and enhanced international collaboration to optimize precision-driven tumor immunotherapy.