osimertinib + pemetrexed + platinum chemotherapy

The combination of osimertinib, pemetrexed, and platinum-based chemotherapy (either cisplatin or carboplatin) is an approved first-line treatment regimen for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations. Developed primarily by AstraZeneca, this combination regimen pairs the third-generation, CNS-active EGFR tyrosine kinase inhibitor (TKI) osimertinib with standard cytotoxic chemotherapy. Osimertinib selectively and irreversibly inhibits both sensitizing EGFR mutations and the T790M resistance mutation. Pemetrexed is a folate antimetabolite that inhibits key enzymes in DNA synthesis, including thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT). The platinum agents (cisplatin or carboplatin) induce DNA cross-linking, leading to cell cycle arrest and apoptosis. This combination strategy aims to delay the onset of resistance and eliminate heterogeneous tumor subclones, significantly improving progression-free survival (PFS) and overall survival (OS) compared to osimertinib monotherapy, as demonstrated in the Phase III FLAURA2 trial.

Other names

OPPOPP regimenTagrisso + Alimta + PlatinolTagrisso + Alimta + carboplatinTagrisso + Alimta + cisplatinTagrisso + pemetrexed + carboplatinTagrisso + pemetrexed + cisplatinTagrisso + pemetrexed + platinumosimertinib + pemetrexed + carboplatinosimertinib + pemetrexed + cisplatinosimertinib + platinum-pemetrexedosimertinib plus pemetrexed plus carboplatinosimertinib plus pemetrexed plus cisplatinosimertinib plus platinum-pemetrexedosimertinib plus platinum-pemetrexed chemotherapy