The negative impact of opioids on cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis

Purpose As one of the most effective analgesics, opioids are essential for patients with cancer-related pain, even in the context of the opioid abuse crisis. The current meta-analysis aimed to identify whether concomitant exposure to opioids can affect the efficacy of ICIs and lead to a worse prognosis.Methods PubMed, Embase, and the Cochrane Library were searched based on the PRISMA checklist, through April 2022, for the following terms: ( "opioids " OR "concomitant medication ") AND ( "Neoplasm " OR "Carcinoma " OR "Cancer " OR "Tumor ") AND ( "Immunotherapy " OR "Immune Checkpoint Inhibitor " OR "PD-L1 Inhibitor " OR "PD-1 Inhibitor " OR "CTLA-4 Inhibitor "). The outcomes considered were overall survival (OS) and progression-free survival (PFS) calculated using the random-effects or fixed-effects model.Results After screening 531 studies, a total of 7 articles involving 2690 patients were eligible for quantitative analysis. The use of opioids was negatively correlated with OS (HR 1.75, 95%CI 1.32-2.31, P < 0.001; I-2= 81%, P < 0.001) and significantly reduced the PFS (HR 1.61, 95%CI 1.41-1.83, P < 0.001; I-2 = 0%, P = 0.63) of patients treated with ICIs. Similar results were obtained in each subgroup analysis. While NSAIDs could lead to poor OS (HR 1.25, 95% CI 1.03-1.51, P = 0.02; I-2 = 0%, P = 0.60) but not PFS (HR 1.11, 95% CI = 0.89-1.39, P = 0.36) for ICIs patients. And sensitivity analyses confirmed the reliability of the results.Conclusion Opioids significantly reduced OS and PFS in patients receiving ICI therapy. Thus, the use of different types of opioids should be considered with caution, and it is necessary to actively develop alternative treatments.