afatinib + osimertinib + carboplatin + pemetrexed

This is a combination regimen consisting of four drugs: afatinib, osimertinib, carboplatin, and pemetrexed. Afatinib and osimertinib are both small molecule tyrosine kinase inhibitors targeting the epidermal growth factor receptor (EGFR), but with different generations and mutation selectivity. Carboplatin is a platinum-based chemotherapeutic agent that induces DNA crosslinking leading to apoptosis, while pemetrexed is an antifolate chemotherapy that inhibits multiple enzymes involved in nucleotide synthesis. This combination has been investigated primarily for the treatment of advanced non–small-cell lung cancer (NSCLC) harboring EGFR mutations, particularly in cases refractory to first-line EGFR TKI therapy such as osimertinib or as part of first-line regimens aiming to overcome resistance mechanisms[1][2][4]. The rationale for combining these agents includes dual blockade of EGFR signaling pathways and cytotoxic effects from chemotherapy to improve efficacy against resistant tumor clones.