Treatment Options for Advanced Non-Small Cell Lung Cancer After Failure of Previous Immune Checkpoint Inhibitors and Chemotherapy: Meta-Analysis of Five Randomized Controlled Trials.

BACKGROUND

Immune checkpoint inhibitors (ICIs), either alone or in combination with platinum-based chemotherapy, are effective in the first-line treatment of metastatic, non-oncogene-addicted, non-small cell lung cancer (NSCLC). However, when NSCLC patients progress, the efficacy of available treatment options is limited.

METHODS

We undertook a meta-analysis that compared combination regimens with the current standard of care. Only randomized controlled trials (RCTs) were included (endpoint, overall survival [OS]). Our analysis used an artificial intelligence software program that reconstructs individual patient data from Kaplan-Meier curves. Hazard ratio (HR) with 95% confidence interval (CI) was the main parameter. Heterogeneity was based on Wald's test and likelihood ratio test.

RESULTS

Five RCTs were included, whose experimental arms included five different combinations. In our analysis, these combination regimes showed no OS benefit compared to chemotherapy (HR = 1.066, 95%CI, 0.9311 to 1.221; = 0.35). Among the five control arms, cross-trial heterogeneity was remarkably low (likelihood ratio test = 3.76 on 4 df, = 0.40; Wald test = 3.83 on 4 df, = 0.40.

DISCUSSION

In conclusion, five new second-line combination treatments for patients with NSCLC were not found to determine any benefit in terms of OS in comparison with the current standard of care.