INDIRECT COMPARISON OF THE EFFICACY OF ERLOTINIB VERSUS PEMETREXED PLUS CISPLATIN AS FIRST LINE TREATMENT IN PATIENTS WITH METASTATIC NON SMALL CELL LUNG CANCER WITH EPIDERMAL GROWTH FACTOR RECEPTOR ACTIVATING MUTATIONS

OBJECTIVES: Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that has proven, in controlled clinical trials, to be effective in the first-line treatment of patients with advanced or metastatic non-small-cell lung cancer (mNSCLC) with EGFR activating (EGFR+) mutations, showing significant improvement of progression-free survival over platinum-based standard chemotherapy. In those trials, pemetrexed was not included in the platinum-based chemotherapy regimens used as a comparator, since it was not yet approved for first line use. Following approval as first line treatment for lung adenocarcinoma, plus cisplatin, it became the standard for this indication. The aim of this analysis was to compare the efficacy in reducing the risk of disease progression for patients with mNSCLC with EGFR+ mutations treated with erlotinib versus pemetrexed/ cisplatin. METHODS: In the absence of head-to-head trials comparing erlotinib with pemetrexed/ cisplatin, an indirect comparison methodology was performed using the Hazard Ratio (HR) - the most appropriate measure to compare time related outcomes. Clinical data was collected from EURTAC and JMDB clinical trials, which compared erlotinib and pemetrexed/ cisplatin, respectively, with different doublet chemotherapy regimens. Assumptions were used to allow this indirect comparison, namely, pemetrexed/ cisplatin relative efficacy observed in JMDB adenocarcinoma patients also applies to patients with EGFR+ mutations and that different doublet chemotherapy regimens used in the mentioned trials are of equivalent efficacy. RESULTS: The HR for disease progression of erlotinib versus pemetrexed/ cisplatin, in patients with mNSCLC and EGFR+ mutations was 0.41 (95% CI: 0.27–0.62, p<0.001). This is equivalent to a 59% reduction in the risk of disease progression. CONCLUSIONS: Despite some limitations and uncertainties associated with indirect comparisons, erlotinib presents itself as a significantly more effective first-line treatment for mNSCLC patients with EGFR+ mutations, showing a significant disease progression risk reduction when compared to pemetrexed/ cisplatin.