Meta-Analysis Sheds Light on Treatment-Related AEs for PD-1 and PD-L1 Inhibitors

Brittany Lovely
Published: Wednesday, May 22, 2019
Yucai Wang, MD

Yucai Wang, MD

Two in 3 patients treated with PD-1 or PD-L1 inhibitors experienced at least 1 adverse event (AE) and 1 in 7 patients experienced at least 1 grade ≥3 AE, according to a systematic review and meta-analysis of clinical trials and study updates published through December 15, 2018.1 Investigators looked at treatment-related AEs of FDAapproved PD-1 and PD-L1 inhibitors to determine important differences between agents and cancer types. The data were compiled from 125 trials involving 20,128 patients published in PubMed, Web of Science, Embase, and Scopus.

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Table. Mean Incidences of AEs by Cancer Type

Table. Mean Incidences of AEs by Cancer Type In addition to pembrolizumab and nivolumab, the PD-L1 inhibitors atezolizumab (Tecentriq), avelumab (Bavencio), and durvalumab (Imfinzi) were used in all the trials included in the meta-analysis. Investigators found that among the 125 studies, 112 (89.6%) reported whether treatment-related deaths occurred. A total of 82 treatment-related deaths were reported (incidence, 0.45%), and 40 studies reported at least 1 treatment-related death.

The authors recommend that although fatigue is not likely to present as severe, because of its high incidence (1 in 5 patients), it should be disclosed as an AE to patients before therapy begins. Although less likely to present as a severe AE in patients, pruritus, diarrhea, and rash are the next most common AEs (about 1 in 10 patients) that clinicians might consider counseling patients about. The authors added that early detection of symptoms, including dyspnea, diarrhea, and alanine aminotransferase or AST, can prevent the development of more severe AEs such as pneumonitis, colitis, and hepatitis.
Wang Y, Zhou S, Yang F, et al. Treatment-related adverse events of PD-1 and PD-L1 inhibitors in clinical trials: a systematic review and meta-analysis [published online April 25, 2019]. JAMA Oncol. doi: 10.1001/jamaoncol.2019.0393.

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