Rheumatic immune-and nonimmune-related adverse events in phase 3 clinical trials assessing PD-(L)1 checkpoint inhibitors for lung cancer: A systematic review and meta-analysis - 29/06/22
, Alvise Berti e, h, iHighlights |
• | Rheumatic immune-related adverse events (i.e. inflammatory arthritis, polymyalgia-rheumatica, myositis, vasculitis) due to PD-(L)1 inhibitors for lung cancer seems to be underreported or misclassified in phase III clinical trials. |
• | Among rheumatic adverse events classified as nonimmune-related, back pain is significantlty associated with PD-(L)1 immune-checkpoint inhibitors, regardless its severity. |
• | Arthralgia is significantly associated with PD-(L)1 immune-checkpoint inhibitors only when they are added on conventional chemotherapy. |
Abstract |
Objectives |
We aimed to analyze rheumatic immune-related (ir) and nonimmune-related adverse events (AEs) due to immune-checkpoint inhibitors (ICIs) targeting programmed cell death-1 or its ligand PD-(L)1 in lung cancer patients from the available literature.
Methods |
We performed a systematic review and meta-analysis of phase III randomized clinical trials (RCTs) assessing PD-(L)1-ICIs in lung cancer patients, from inception until January 12th, 2021. We extracted data of each trial to estimate odds ratio (OR) for rheumatic ir or non-irAE as classified in RCTs safety data. Sensitivity analyses (by ICI, treatment group and histology) were performed.
Results |
Eighteen RCTs met the inclusion criteria (n=12172 subjects). The OR [95%IC] for rheumatic irAE in ICIs versus controls (either placebo or chemotherapy) was 2.20 [0.85,5.72]. Among rheumatic non-irAEs, both overall and severe (grade≥3) back pain were significantly more frequent in ICIs versus controls, 2.01 [1.09;3.73] and 2.90 [1.18;7.08], respectively. The overall frequency of arthralgia was similar between ICIs and controls; by sensitivity analysis RCTs assessing ICIs in combination with chemotherapy showed a significant association with arthralgia (1.55 [1.15;2.10]). Similarly, the frequency of myalgia was significantly lower in RCTs assessing ICIs alone versus chemotherapy (OR 0.32 [0.24;0.42]). Muscular pain was not significantly increased with ICI.
Conclusion |
Rheumatic irAEs are not increased in RCTs assessing PD-(L)1 inhibitors, not reflecting the real-life incidence, therefore likely underreported or misclassified. Back pain is significantly associated with them regardless its severity, while arthralgia only when ICIs are added on conventional chemotherapy.
El texto completo de este artículo está disponible en PDF.Keywords : Arthralgia, Rheumatic adverse events, Lung cancer, Immune related adverse event, Meta-analysis, Immune checkpoint inhibitors, Randomized clinical trials
Esquema
Vol 89 - N° 4
Artículo 105403- juillet 2022 Regresar al número
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