Background and clinical significance of biomarker-based patient enrichment in non-small-cell lung cancer drug development.

Pharmaceutical companies have adopted biomarker-based enrichment (personalized) strategies to improve research and development productivity. We explored the background in which personalized strategies are adopted and examined whether their adoption is linked to improved efficacy of new drugs approved for non-small cell lung cancer (NSCLC) by US Food and Drug Administration (FDA). We extracted data from the first labels of drugs approved for NSCLC between May 2003 and February 2021, and performed a qualitative comparative analysis and meta-analysis. Personalized strategies were adopted in more than half of the trials (16/27) and were often used in trials aimed at obtaining first-line indications and in drugs that were not first-in-class. The meta-analysis showed that personalized trials had significantly improved progression-free survival (PFS) hazard ratio (HR) than trials without personalization but not for relative response rate ratio (RRR) or overall survival (OS) HR. Trials in which PFS HR was the primary endpoint tended to have improved PFS HR, and trials in which OS HR was the primary endpoint had worse PFS HR. The efficacy endpoints that are substantially affected by personalized strategies appear to differ, especially for new drugs with novel mechanism of action (MOA), because trial designs are employed to validate drug-specific advantages.