First‐line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive non‐squamous non‐small cell lung cancer

Background Epidermal growth factor receptor (EGFR) mutation positive (M+) non‐small cell lung cancer (NSCLC) is emerging as an important subtype of lung cancer comprising 10% to 15% of non‐squamous tumours. This subtype is more common in women than men and is less associated with smoking. Objectives To assess the clinical effectiveness of single ‐agent or combination EGFR therapies used in the first‐line treatment of people with locally advanced or metastatic EGFR M+ NSCLC compared with other cytotoxic chemotherapy (CTX) agents used alone or in combination, or best supportive care (BSC). The primary outcome was overall survival. Secondary outcomes included progression‐free survival, response rate, toxicity, and quality of life. Search methods We conducted electronic searches of the the Cochrane Register of Controlled Trials (CENTRAL) (2015, Issue 6), MEDLINE (1946 to 1 June 2015), EMBASE (1980 to 1 June 2015), and ISI Web of Science (1899 to 1 June 2015). We also searched the conference s of the American Society for Clinical Oncology and the European Society for Medical Oncology (1 June 2015); Evidence Review Group submissions to the National Institute for Health and Care Excellence; and the reference lists of retrieved articles. Selection criteria Parallel randomised controlled trials comparing EGFR‐targeted agents (alone or in combination with cytotoxic agents or BSC) with cytotoxic chemotherapy (single or doublet) or BSC in chemotherapy‐naive patients with locally advanced or metastatic (stage IIIB or IV) EGFR M+ NSCLC unsuitable for treatment with curative intent. Data collection and analysis Two review authors independently identified articles, extracted data, and carried out the 'Risk of bias' assessment. We conducted meta‐analyses using a fixed‐effect model unless there was substantial heterogeneity, in which case we also performed a random‐effects analysis as a sensitivity analysis. Main results Nineteen trials met the inclusion criteria. Seven of these exclusively recruited people with EGFR M+ NSCLC; the remainder recruited a mixed population and reported results for people with EGFR M+ NSCLC as subgroup analyses. The number of participants with EGFR M+ tumours totalled 2317, of whom 1700 were of Asian origin. Overall survival (OS) data showed inconsistent results between the included trials that compared EGFR‐targeted treatments against cytotoxic chemotherapy or placebo. Erlotinib was the intervention treatment used in eight trials, gefitinib in