The following article features coverage from the European Society for Medical Oncology (ESMO) 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Immune-related adverse event (irAE) risks vary between immune checkpoint inhibitors, according to findings from a meta-analysis of data from 35 clinical trial reports, presented at the European Society of Medical Oncology (ESMO) Congress 2019 in Barcelona, Spain.1

“Overall, the risk of grade ≥3 irAEs was higher with anti–PD-1 versus anti–PD-L1 agents,” reported the authors, led by Guru P. Sonpavde, MD, of the Dana-Farber Cancer Institute in Boston, Massachusetts, in the abstract. “Compared with other agents, avelumab had a lower risk of individual grade ≥3 irAEs except elevated AST, whereas atezolizumab had the lowest risk of irAEs of any grade.”

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Six anti–PD-1/PD-L1 immune checkpoint inhibitors have been approved by the US Food and Drug Administration to treat cancers, the authors wrote. However, there are no head-to-head comparisons evaluating the risk of irAEs.

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In order to assess the risks of irAEs across agents, the study authors reviewed data from 35 clinical trial manuscripts representing 8730 patients treated with anti–PD-1 (nivolumab and pembrolizumab) and anti–PD-L1 (atezolizumab, avelumab, and durvalumab) monotherapies. They calculated odds ratios (ORs) for irAEs overall, and for any-grade and grade 3 or higher colitis, elevated AST, hypothyroidism, pneumonitis, and rash.

They found that anti–PD-1 immune checkpoint blockade involved higher risks than anti–PD-L1 agents of any grade and grade 3 or higher irAE rash (ORs, 4.34 and 4.38, respectively), grade 3 or higher irAE hypothyroidism (OR, 2.85), and any grade or grade 3 or higher irAE colitis (ORs, 2.53 and 3.79, respectively), the investigators reported.

“When comparing the risk of all selected irAEs for each agent with pooled estimates for all other agents combined, atezolizumab had the lowest risk, followed by avelumab; pembrolizumab had a higher risk, except for grade ≥3 elevated AST,” they wrote. “In pairwise comparisons, the risks associated with atezolizumab vs avelumab were not significantly different.”

The same was true for nivolumab vs pembrolizumab.

“The largest decrease in risk for all grade ≥3 irAEs except elevated AST was for avelumab vs pembrolizumab,” Dr Sonpavde added.

Meta-analyses are retrospective and this analysis included different study designs, tumor types, treatment durations and irAE evaluations, Dr Sonpavde cautioned.

Disclosure: The study was funded by Merck Healthcare KGaA and Pfizer Inc, and some of the authors disclosed payments from various pharmaceutical and medical companies. For a full list of disclosures, please refer to the abstract.

Read more of Cancer Therapy Advisor‘s coverage of the ESMO annual meeting by visiting the conference page.


Sonpavde GP, Grivas P, Lin Y, Hennessy D, Hunt JD. Immune-related adverse events (irAEs) with single-agent PD-1 vs PD-L1 inhibitors: A meta-analysis of 8,730 patients from clinical trials. Presented at: European Society of Medical Oncology (ESMO) Congress 2019; September 27-October 1, 2019: Barcelona, Spain. Abstract 1297P.