1276PFIRST-LINE TREATMENT OF ADVANCED EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) MUTATION POSITIVE (M+) NON-SQUAMOUS NON-SMALL CELL (NSCLC) LUNG CANCER – A COCHRANE COLLABORATION META-ANALYSIS

Abstract Aim: To systematically review the outcome of treatment of the EGFR M+ NSCLC subtype. Measures studied are overall survival (OS), progression free survival (PFS), response and QOL/symptom control. Methods: EGFR-targeted agents (alone or in combination with cytotoxic agents or best supportive care (BSC)) were compared with cytotoxic chemotherapy (CTX), (alone or in combination with EGFR-targeted therapies or BSC) in randomised controlled trials. All patients in the trials were CTX-naive with locally advanced or metastatic (Stage IIIB or IV) EGFR M+ NSCLC unsuitable for treatment with curative intent. Results: Eighteen trials accruing a total of 2085 EGFR M+ patients met the inclusion criteria; 1343 were from Asian countries. Six of these trials exclusively recruited 1455 patients with EGFR M+ NSCLC, the remaining trials recruited a mixed population and reported results for patients with EGFR M+ NSCLC as subgroup analyses. Erlotinib was the intervention treatment in 8 trials, gefitinib in 6 trials, afatinib in 2 trials and cetuximab in 2 trials. Only one trial (FASTACT2; n = 97) demonstrated an OS benefit and favoured erlotinib + gemcitabine + platinum over gemcitabine + platinum. For PFS, a pooled analysis of 3 studies (EURTAC, OPTIMAL, TORCH; n = 378) demonstrated a clear benefit of erlotinib compared with CTX (HR = 0.30; 95% CI: 0.23 to 0.40). In a pooled analysis, two studies (IPASS, NEJSG; n = 491) demonstrated a clear PFS benefit of gefitinib compared with paclitaxel + carboplatin (HR = 0.39; 95% CI: 0.32 to 0.48). The two trials featuring afatinib (LUX-lung 3, LUX-lung 6; n = 709) showed a pooled PFS benefit in favour of afatanib when compared with CTX (HR = 0.42; 95% CI: 0.34 to 0.53). No statistically significant PFS benefit for cetuximab + CTX was reported in the two trials of cetuximab (FLEX, BMS099; n = 81). Commonly reported adverse events for erlotinib, gefitinib and afatinib were rash, diarrhoea and mucositis. Quality of life and symptom control were reported differently across six trials. Conclusions: Erlotinib, gefitinib or afatinib should be the first-line treatment of choice for EGFR M+ NSCLC. Cytotoxic CTX alone is less effective than erlotinib, gefitinib or afatinib and produces greater toxicity in this population. Disclosure: All authors have declared no conflicts of interest.