Osimertinib in combination with anti-angiogenesis therapy presents a promising option for osimertinib-resistant non-small cell lung cancer – BMC Medicine
Background Osimertinib has become standard care for epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) patients whereas drug resistance remains inevitable. Now we recognize that the interactions between the tumor and the tumor microenvironment (TME) also account for drug resistance. Therefore, we provide a new sight into post-osimertinib management, focusing on the alteration of TME. Methods We conducted a retrospective study on the prognosis of different treatments after osimertinib resistance. Next, we carried out in vivo experiment to validate our findings using a humanized mouse model. Furthermore, we performed single-cell transcriptome sequencing (scRNA-seq) of tumor tissue from the above treatment groups to explore the mechanisms of TME changes. Results Totally 111 advanced NSCLC patients have been enrolled in the retrospective study. The median PFS was 9.84 months (95% CI 7.0–12.6 months) in the osimertinib plus anti-angiogenesis group, significa