Dacomitinib/dacomitinib combined with osimertinib

Dacomitinib/Dacomitinib and Osimertinib are both important therapeutic drugs for EGFR mutated non-small cell lung cancer, and both have been approved as first-line treatment options for this type of cancer. However, when these drugs are used alone, patients may develop resistance, affecting the effectiveness of treatment. In order to solve this problem, researchers began to explore the possibility of combining dacomitinib and osimertinib.

Osimertinib, as a third-generation irreversibleEGFR TKI, has become the standard first-line treatment for patients with EGFR-mutated lung cancer. It was originally developed to treat acquired EGFR T790M mutations, the most common cause of resistance to early EGFR TKIs. Compared with the first-generation EGFR TKI, osimertinib shows better efficacy in early treatment and can improve patients' progression-free survival and overall survival. However, resistance to osimertinib has gradually emerged, among which the acquired second-site mutation of EGFR at EGFR C797S (the binding site of osimertinib and EGFR) is the cause of some common drug resistance.

Dacomitinib, as a panHER tyrosine kinase inhibitor, has also been proven to be effective in the first-line treatment of patients with EGFR mutant lung cancer. In the ARCHER 1050 study, compared with gefitinib, the median progression-free survival of dacomitinib as a first-line treatment reached 14.7 months, which was significantly higher than gefitinib's 9.2 months. For first- and second-generation EGFR inhibitors, the most common resistance mechanism is the acquisition of the second-site mutation EGFR T790M.

Based on these findings, the researchers proposed a hypothesis: the combination of dacomitinib and osimertinib may be able to effectively prevent the observed acquired EGFR mutation spectrum, thereby becoming an effective first-line treatment option for patients with advanced EGFR-mutated lung cancer. Specifically, osimertinib is effective against EGFR T790M, while dacomitinib is effective against EGFR C797S. This hypothesis is consistent with previous studies showing that combination targeted therapies can delay the emergence of acquired drug resistance in EGFR-mutated lung cancer.

However, it is important to note that the combination of dacomitinib and osimertinib has not yet been clinically approved. Therefore, its efficacy and safety still need to be further verified through clinical trials. In clinical trials, researchers will evaluate the efficacy, safety, and patient tolerability of the combination. This treatment regimen will be recommended for clinical practice only if it is well demonstrated that the benefits of a combination clearly outweigh the potential risks. Therefore, no matter which treatment option a patient chooses, he or she should strictly follow the doctor's recommendations and instructions and use the drug in accordance with the prescribed dosage and usage.