apatinib and osimertinib

The combination of apatinib and osimertinib represents a dual-targeted approach for treating non-small cell lung cancer (NSCLC), particularly in patients who have developed resistance to osimertinib monotherapy. Apatinib is a VEGFR inhibitor, and osimertinib is a third-generation EGFR inhibitor, enabling this combination to target both EGFR mutations and VEGF pathways simultaneously. In clinical studies involving EGFR-mutant NSCLC patients who developed resistance to osimertinib, this combination demonstrated an overall response rate (ORR) of 12.8% and a disease control rate (DCR) of 79.5%. The median progression-free survival (PFS) was approximately 4 months, with a 6-month PFS rate of 38%. Laboratory studies have confirmed that apatinib enhances the anti-tumor activity of osimertinib in T790M positive lung adenocarcinoma cell lines and xenograft models. This combination is primarily being investigated for osimertinib-refractory EGFR-mutant NSCLC, targeting specific resistance mechanisms including MET amplification, PIK3CA mutations, PTEN loss-of-function, ERBB2 amplification, and IGF1R mutations. The most common adverse events observed include hypertension (30.7%), diarrhea (15.4%), and proteinuria (12.8%). While it increases the risk of treatment-emergent adverse events compared to single-agent therapy, no unexpected safety signals have been identified. This dual oral regimen is considered feasible and safe, potentially offering clinical benefit, especially in patients with MET amplification, and a convenient treatment option.