Mechanisms of resistance to first-generation EGFR-TKIs are widely known and include for the majority of cases the onset of the second-site EGFR mutation substituting threonine for methionine at position 790 in exon 20 (T790M), the activation of other cellular signaling such as MET [4], ERBB2, AXL [5], Hedgehog (Hh) [6] or of downstream escape mediators (BRAF, PIK3CA) and histological changes as epithelial-to-mesenchymal transition (EMT) and small cell lung cancer (SCLC) [7, 8]. This evidence concerns the gene PIK3CA and small cell lung carcinoma.