As reported in The Lancet Oncology by Zhao et al, meta-analyses of trials of immune checkpoint inhibitors (ICIs) in patients with advanced EGFR-mutated non–small cell lung cancer (NSCLC) progressing on EGFR tyrosine kinase inhibitor (TKI) treatment indicate that the optimal treatment strategy is use of combined ICI, antiangiogenesis therapy, and chemotherapy.
Study Details
A total of 32 single-arm or randomized controlled trials involving 2,886 patients were assessed for seven different ICI-based strategies. The outcome measure of interest was progression-free survival.
Key Findings
Three strategies had sufficient data to perform a pairwise meta-analysis. In this analysis, compared with chemotherapy alone, ICI monotherapy was associated with poorer progression-free survival (hazard ratio [HR] = 1.73, 95% confidence interval [CI] = 1.30–2.29), and regimens of ICI/antiangiogenesis/chemotherapy (HR = 0.54, 95% CI = 0.44–0.67) and ICI/chemotherapy (HR = 0.77, 95% CI = 0.67–0.88) were associated with better progression-free survival.
Network meta-analysis showed that ICI/antiangiogenesis/chemotherapy was associated with better progression-free survival compared with ICI/chemotherapy (HR = 0.71, 95% credible interval [CrI] = 0.59–0.85), ICI monotherapy (HR = 0.30, 95% CrI = 0.22–0.41), and non-ICI treatment strategies including antiangiogenesis/chemotherapy (HR = 0.76, 95% CrI = 0.58–1.00) and chemotherapy alone (HR = 0.54, 95% CrI = 0.45–0.64).
In network meta-analysis, ICI/antiangiogenesis/chemotherapy was associated with greater risks of any-grade and grade ≥ 3 adverse events vs ICI/chemotherapy and chemotherapy alone.
The investigators concluded, “For individuals with advanced EGFR-mutated NSCLC who progressed on EGFR TKIs, ICI/antiangiogenesis/chemotherapy was identified as the optimal treatment option. The toxicity of this treatment was acceptable but needs careful attention. ICI-chemotherapy showed appreciably greater efficacy than the standard-of-care chemotherapy. These findings clarified the roles of ICI-based treatment strategies in this difficult-to-treat refractory population, potentially complementing recent guidelines.”
Jianxing He, MD, of the Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Centre for Respiratory Disease, Guangzhou, is the corresponding author for The Lancet Oncology article.
Disclosure: The investigators reported that there was no external funding for the study. For full disclosures of the study authors, visit thelancet.com.
