Effect of pretreatment with dexamethasone on the efficacy and immune-related adverse events of immunotherapy in first-line treatment for advanced non-small cell lung cancer: a network meta-analysis of randomized control trials.

Background: The pretreatment of dexamethasone on the efficacy and immune-related adverse events of immunotherapy involving programmed cell death 1/programmed cell death 1 ligand 1 (PD1/PDL1) inhibitors is an effective option for the first-line treatment of advanced non-small-cell lung cancer (NSCLC). With the immunosuppressive effect, corticosteroids may be used to reduce the efficacy of PDL1 blockade, as well as prevent overactive immune responses, thereby reducing the occurrence of immune-related adverse events (irAEs). This study quantitatively summarized the current evidence, and compared the efficacy and toxicity of therapies involving chemotherapy plus PDL1 inhibitors plus dexamethasone pretreatment (I+C+D) with chemotherapy plus PDL1 inhibitors (I+C) and therapies involving PDL1 inhibitors or chemotherapy alone (I or C).

Methods: The protocol of this study was registered with PROSPERO (CRD42021227281). By using a network meta-analysis approach, the different treatments were compared and ranked based on their effectiveness and rates of irAEs at the different grades. Risk rates were determined through direct meta-analysis and indirect treatment comparison.

Results: 12 randomized clinical trials were included with a total of 7155 NSCLC patients. Network meta-analysis generated 15 comparisons. The combination treatment of I+C+D showed a longer progression-free survival and overall survival, while I+C was less toxic, and the toxicity of I+C+D or that of I+C had been significantly decreased, compared to that of monotherapy with either drug. According to the ranking analysis, I+C+D is consistently proved to be the most effective therapeutic strategy, while I+C is linked to the lowest rate of irAEs, with the rate of grade value of ≥3 irAEs.

Conclusion: The combination treatment of I+C+D is the most effective approach for the first-line treatment of NSCLC patients treated with I+C, I, or C.