However, so far, there are no reports about the other irreversible EGFR-TKIs resistance based on PIK3CA alteration [19, 34], While in a case report, a patient with EGFR L858R/T790M/PIK3CA mutation after progressing on erlotinib did not response to afatinib plus cetuximab treatment which was effective in preclinical model and NSCLC patients with T790M mutation. The gene discussed is EGFR; the disease is non-small cell lung carcinoma.