Immunotherapy with PD-1 and PD-L1 inhibitors has been a welcome addition to cancer treatment across numerous tumor types. While these agents are highly effective in some patients, they can be associated with severe, long-lasting adverse events (AEs). To better capture the incidence of AEs associated with PD-(L)1 inhibitors, a recent meta-analysis published in JAMA Oncology evaluated rates and types of AEs associated with PD-(L)1 inhibitor monotherapy across 125 clinical trials that included 20,128 patients with cancer. Interestingly, this analysis found that while most patients (66%) experienced an AE, AEs of grade 3 or higher were uncommon, occurring in only 14% of patients. The most common AEs of any grade were fatigue, pruritus, and diarrhea, while fatigue, anemia, and aspartate aminotransferase level elevations were the most common grade 3 or higher AEs. Although none of the agents were compared head-to-head in a clinical trial, some cross-trial comparisons were made. The authors noted that patients receiving nivolumab were slightly more likely to experience an AE than those receiving pembrolizumab (odds ratio 1.28), and grade 3 or higher AEs occurred more frequently with PD-1 inhibitors compared with PD-L1 inhibitors (odds ratio 1.58). However, it is important to note that these comparisons do not take into account the fact that studies of the more recent agents benefited from protocols to monitor and manage the expected AEs based on experiences gained in studies of the earlier agents.
High Altitude: This meta-analysis is the largest study to-date of treatment-related AEs associated with PD-(L)1 inhibitors, and provides valuable information regarding the expected AE profiles. It also provides some insight into potential differences between the agents. This may aid in design of better monitoring strategies and treatment algorithms. However, as a meta-analysis, this study is limited in its impact because of the lack of head-to-head comparison and the pooling of data from different malignancies.
Ground Level: As immunotherapies become standard treatments across multiple tumor types, it is increasingly important for clinicians to be comfortable administering these agents and familiar in managing their unique AE profiles. This meta-analysis provides important information to oncologists on the common profile of treatment-related AEs in patients receiving PD-(L)1 inhibitors. However, in practice, the product labels remain the cornerstones for information on the types of AEs associated with each agent in different tumor types. Awareness of the signs and symptoms of these toxicities could allow for earlier intervention and—potentially—more effective management.