Impact of corticosteroid use on outcomes of non–small‐cell lung cancer patients treated with immune checkpoint inhibitors: A systematic review and meta‐analysis

Abstract

What is known and objective Administration of corticosteroids to immune checkpoint inhibitors (ICI)–treated patients has raised concerns due to doubts about ICIs' efficacy under those conditions. Hence, we reviewed studies comparing overall and progression‐free survival (OS and PFS) outcomes in patients with non–small‐cell lung carcinoma (NSCLC) treated with ICI and either with or without corticosteroids for any reason. Methods We searched the PubMed Central, Cochrane library, EMBASE and MEDLINE databases from inception until February 2021 for relevant publications. We used the Newcastle‐Ottawa scale to assess the quality of the identified studies. We used the published data to carry out a meta‐analysis with a random‐effects model and report pooled odds ratios (ORs) with 95% confidence intervals (CIs). Results We included data from 14 studies with 5461 participants in the meta‐analysis. Most studies were retrospective in nature and of low quality, and most of them were conducted in the USA and in European countries. Nivolumab is the most common ICI used in the included studies followed by pembrolizumab. We found that patients using corticosteroids had reduced OSs (pooled HR, 1.82; 95% CI, 1.51–2.18) and PFSs (pooled HR, 1.69; 95% CI, 1.41–2.04) than the patients not using corticosteroids. We identified significant heterogeneity and publication bias for both the outcomes. However, the sensitivity analysis revealed that the estimates were robust to the individual study effects. What is new and conclusion Our findings suggest that corticosteroids significantly reduce the OS and PFS of patients with NSCLC under ICI therapy. Hence, clinicians and oncologists should consider this information when prescribing corticosteroids for this target population.

Impact of concurrent medications on clinical outcomes of cancer patients treated with immune checkpoint inhibitors: analysis of Health Insurance Review and Assessment data

“…They are commonly used by patients with cancer and transplant recipients, making immunosuppression-induced dysbiosis a topic of research in transplant settings (Colard-Thomas et al 2023 ; Chong and Koh 2020 ). Some meta-analyses have reported negative effects of CSs on the survival of patients treated with ICIs (Petrelli et al 2020 ; Zhang et al 2021 ). It should be noted that patients requiring high doses of steroids, such as those with palliative reasons or brain metastases, may have pre-existing conditions that make them vulnerable to poor prognoses, which could be a confounding factor that cannot be excluded (Jessurun et al 2021 ).…”

Safety and efficacy of immune checkpoint inhibitors in advanced cancer patients with autoimmune disease: A meta-analysis

“…Since only two studies have discussed the use of immunosuppressants to control irAEs, we cannot rely on the limited data to accurately analyze results [15,19] . Zhang et al found that the OS and PFS were signi cantly shortened in the administration of corticosteroids [32] . However, Fausto et al indicated that the use of steroids in cancer patients to control irAEs did not shorten OS [33,34] .…”

The role of kidney biopsy in immune checkpoint inhibitor nephrotoxicity

“…One study noted that even an average of 6 days of oral corticosteroids (maximal dose, 40 mg/day) was associated with an increased incidence of diabetes mellitus, sepsis, venous thromboembolism, and fractures ( 52 ). Furthermore, a meta-analysis suggested that corticosteroids may also blunt the efficacy of ICPIs in patients with non-small cell lung cancer ( 53 ). Premature discontinuation of ICPI therapy without confirmatory testing can negatively impact treatment outcomes by halting a potentially life-saving treatment.…”