Treatment-Related Adverse Events With PD-1/PD-L1 Inhibitors in Clinical Trials
In a systematic review and meta-analysis reported in JAMA Oncology, Wang et al characterized treatment-related adverse event profiles associated with monotherapy use of programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors in clinical trials.
Study Details
Studies eligible for inclusion in the analysis had to meet the following criteria: cancer therapy clinical trial; patients were treated with a single-agent PD-1 or PD-L1 inhibitor; tabulated data on treatment-related adverse events were reported; and the study was published in English.
The analysis included 125 clinical trials involving 20,128 patients treated with PD-1 (eg, nivolumab and pembrolizumab) or PD-L1 inhibitors (eg, atezolizumab, avelumab, and durvalumab).
Key Findings on Treatment-Related Adverse Events
- Overall, 12,277 (66.0%) of 18,610 patients from 106 studies had ≥ 1 treatment-related adverse event of any grade, and 2,627 (14.0%) of 18,715 patients from 110 studies had ≥ 1 treatment-related adverse event of grade ≥ 3.
- The most common any grade adverse events were fatigue (18.26%), pruritus (10.61%), and diarrhea (9.47%).
- The most common grade ≥ 3 adverse events were fatigue (0.89%), anemia (0.78%), and increased aspartate aminotransferase (0.75%).
- Hypothyroidism (6.07%) and hyperthyroidism (2.82%) were the most common all-grade endocrine immune-related adverse events.
- Nivolumab was associated with numerically higher mean incidence of any grade adverse events (odds ratio [OR] = 1.28, 95% confidence interval [CI] = 0.97–1.79) and grade ≥ 3 adverse events (OR = 1.30, 95% CI = 0.89–2.00) vs pembrolizumab.
- PD-1 inhibitors were associated with a borderline significant higher mean incidence of grade ≥ 3 adverse events compared with PD-L1 inhibitors (OR = 1.58, 95% CI = 1.00–2.54).
The investigators concluded, “Different PD-1 and PD-L1 inhibitors appear to have varying treatment-related adverse events; a comprehensive summary of the incidences of treatment-related adverse events in clinical trials provides an important guide for clinicians.”
Michael L. Wang, MD, of the Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, is the corresponding author for the JAMA Oncology article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
