Abstract
Recent advances in the treatment of non-small cell lung cancer (NSCLC) have led to improvements in patient survival and quality of life. It is unclear whether molecular abnormalities associated with NSCLC cell survival, growth and proliferation are useful in predicting treatment benefit. We conducted a systematic review to establish which biomarkers contribute meaningfully to the management of NSCLC. A team of researchers searched PubMed and conference proceedings (ASCO, ESMO, IASLC, USCAP) using MESH terms for NSCLC and randomized trials (RCT), plus keywords for variables of interest. Evidence from multiple RCTs confirmed that histologic subtype is prognostic for survival and predictive of treatment efficacy and/or toxicity in NSCLC. Likewise, activating mutations of the epidermal growth factor receptor (EGFR) are associated with benefit from EGFR tyrosine kinase inhibitors in patients with advanced non-squamous NSCLC and should be assessed routinely. No biomarkers to date reliably predict response to anti-Vascular Endothelial Growth Factor (VEGF) therapies. There are inconsistent data on the role of ERCC1, BRCA, Beta tubulin III, RRM1, K-RAS, or TP-53 in treatment decisions. These tests should not be routinely used in selecting treatment at this time, whereas EML4/ALK translocations predict responses to specific targeted agents, the optimal assessment of this molecular abnormality has yet to be established. Personalized care of patients with NSCLC based on biomarkers is increasingly important to both clinical practice and research.
Highlights
Significant progress has been made in the treatment of non-small-cell lung cancer (NSCLC) over the last three decades
There is consistent information from three randomized trials (Table 1) that histology is predictive of the benefit from pemetrexed, a multi-targeted anti-folate, which primarily inhibits thymidylate synthase (TS) [15]
There was a significant treatment by histology quantitative interaction whereby patients with nonsquamous histology had markedly longer progression free survival (PFS)
Summary
Significant progress has been made in the treatment of non-small-cell lung cancer (NSCLC) over the last three decades. Attempts to improve outcomes in NSCLC have resulted in strategies to individualize, or personalize treatment decisions, based on clinically or molecularly defined biomarkers, broadly defined as characteristics that are “objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention” [9]. Potential predictive biomarkers include clinical characteristics, such as performance status, gender, race, and smoking status [7,8,10,11], as well as pathologic features such as histological subtypes of NSCLC [12,13]. We will review the key findings of randomized controlled trials in NSCLC evaluating biomarkers predictive of responses to anti-EGFR, anti-angiogenic, and chemo-therapeutic agents. These interactions include both quantitative effects, in which there are statistically significant differences in effect sizes between subgroups, and qualitative effects, in which the direction in effect size is opposite between subgroups
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