medwireNews: A meta-analysis has shown that cutaneous immune-related adverse events (irAEs) are prognostic for improved survival among people with cancer receiving immune checkpoint inhibitor (ICI) therapy.
The researchers explain that “[a]lthough numerous systematic reviews and meta-analyses have investigated the emergence of irAEs and their association with treatment effectiveness and survival outcomes, there has been a paucity of reviews examining potential associations between [cutaneous] irAE emergence and prognosis among patients receiving ICI treatment.”
Their meta-analysis included 23 studies comprising 22,749 patients treated with ICIs. Nine studies focused on melanoma, seven on non-small-cell lung cancer (NSCLC), one on renal cell cancer, and the remaining six included multiple tumor types. Eight studies each were conducted in the Asia–Pacific region and Europe, while seven were US-based studies.
The analysis for overall survival (OS), which drew on 16 studies, showed a significant 39% reduction in the risk for death among people who did versus did not develop cutaneous irAEs after ICI treatment.
Similarly, pooling data from the 12 studies that reported on progression-free survival (PFS) revealed a significant 48% lower risk for disease progression or death with cutaneous irAEs.
“Consistent results were observed across all subgroups stratified by [cutaneous] irAE subtype, study design, geographic region, ICI type, and cancer type except for PFS analysis in the US,” report Fei Wang and colleagues, from Southeast University in Nanjing, China, in JAMA Dermatology.
For instance, among patients with melanoma, the hazard ratio (HR) for death was a significant 0.51 for those with cutaneous irAEs relative to those without, while the HR for progression or death was a significant 0.45. The corresponding HRs for the NSCLC subgroup were 0.50 and 0.61.
With regard to the subtypes of cutaneous irAEs, the development of vitiligo, lichenoid or lichen planus-like skin lesions, psoriasis, eczema, and pruritus without rash was associated with a significantly reduced risk for death, with HRs of 0.30, 0.51, 0.63, 0.69, and 0.70, respectively. But there was no such significant OS association for bullous pemphigoid and exanthem, and vitiligo was the only cutaneous irAE that conferred a significant PFS advantage, with an HR of 0.28.
Wang and team highlight some of the limitations of the meta-analysis, such as the fact that “the majority of the data came from retrospective studies, adding possible biases such as recall bias and selection bias,” and “the substantial publication bias” revealed by the Egger tests, “suggesting that this may exaggerate the pooled results.”
And they conclude: “More large-scale prospective studies are needed to validate and establish the association between [cutaneous] irAEs and survival outcomes, especially for different grades of [cutaneous] irAEs and interactions with multisystem irAEs.”
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