Integrating biomarkers into clinical trials: methodological issues for a new paradigm in nonsmall cell lung cancer

To summarize the major methodological issues concerning prognostic biomarkers in nonsmall cell lung cancers (NSCLCs) and to discuss integration of biomarkers into clinical trials.

Large phase 3 trials have recently been published in early-resected NSCLC with studies of biomarkers identifying subsets of patients that benefited most from the experimental perioperative strategy. The IALT-bio study reported that ERCC1 DNA-repair protein had prognostic and predictive implications. Other studies reported on the prognostic role of TUBB3 expression in stages I-III NSCLCs. The IPASS study reported the predictive and prognostic impact of epidermal growth factor receptor (EGFR) mutations in stage IV patients treated with EGFR tyrosine kinase inhibitor or platinum-based chemotherapy. Whereas EGFR mutations studies received prospective validation with trials in which treatment allocation was based on biomarker status, chemotherapy biomarkers still need such prospective confirmations, and many biases were still encountered in recent published studies.

Biomarkers of treatment efficacy will help to tailor treatment in NSCLCs. EGFR mutations have reached that point. Markers of chemotherapy efficacy still need validation studies before coming into routine practice. Stringent methodological recommendations should avoid most of the possible pitfalls of those studies and allow clinical applicability of such biomarkers.