medwireNews: The risk for neurologic adverse events (AEs) is significantly lower with immune checkpoint inhibitors (ICIs) than with other cancer treatments, particularly chemotherapy, suggest results of a systematic review and meta-analysis.
The study included data from 39 phase 2 or 3 randomized controlled trials (RCTs) comparing ICI use (anti-PD-1/PD-L1 and/or anti-CTLA-4 therapy) with non-ICI drugs (chemotherapy, targeted therapy, vaccines, or combination therapies) and placebo in 23,705 patients (68.0% men, 33.1% White) with various cancers.
Non-small-cell lung cancer was the most common cancer included in the analysis (n=16 trials), followed by melanoma (n=5), renal cell carcinoma (n=4), and several others (n=1–3 each).
Overall, 15.0% of 10,595 patients who received an ICI alone or in combination with another treatment experienced a neurologic AE compared with 19.9% of 13,110 patients who did not received an ICI.
The difference between the two groups corresponded to a significant 41% lower risk for a neurologic AE with ICI versus other treatment or placebo, report Ankit Mangla (Case Western Reserve University School of Medicine, Cleveland, Ohio, USA) and co-authors in JAMA Network Open.
Among the specific AEs reviewed, the risk for peripheral neuropathy was a significant 70% lower among patients who received an ICI compared with those who received other treatments or placebo (4.2 vs 10.5%), while the risk for dysgeusia was a significant 59% lower (4.9 vs 14.4%). Conversely, individuals treated with ICIs had a significant 32% higher risk for headache (11.6 vs 8.8%) than those treated with other drugs or placebo.
To exclude the potential confounding effect of having chemotherapy in both arms, the researchers performed a second analysis using data from 15 trials that compared ICI use alone with chemotherapy. In this case, the risk for neurologic AEs was a significant 78% lower in the ICI group than in the chemotherapy group, with rates of 6.0% and 17.4%, respectively.
In line with the overall findings, the risks for peripheral neuropathy and dysgeusia were a significant 91% and 58% lower with ICI use relative to chemotherapy. In addition, the risk for paresthesia was a significant 71% lower in the ICI group, but there was no significant difference between the two group in the risk for headache.
Finally, the team showed that the risk for a neurologic AE was a significant 57% higher in the ICI groups than in the placebo groups of five trials with available data.
“These results indicated that although ICI use is associated with an increased risk of [neurologic] AEs [vs placebo], the risk is much lower when compared with chemotherapy,” Mangla et al remark.
They caution, however that “heterogeneity in the comparator arm limits the interpretation of this analysis as several RCTs involved either chemotherapy in both arms or had an immunomodulator, tyrosine kinase inhibitor, or placebo in the comparator arm.”
The researchers also point out that “most of these trials included patients with relapsed refractory neoplasms who have had previous chemotherapy exposure, which could have contributed to the increased incidence of [neurologic] AEs.”
In an accompanying comment, Daniel Vargas Pivato de Almeida, from Grupo Oncoclínicas in Brasília, Brazil, says that in an era where ICIs are being more broadly prescribed, the current study “serves to help us more clearly determine the risks to which we are exposing our patients during treatment with ICIs and to offer more data for our discussions of risk vs benefits with our patients.”
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