Real-world data and circulating tumor DNA (ctDNA) are helping doctors detect and overcome treatment resistance in EGFR-mutated non-small cell lung cancer. Resistance patterns vary by treatment. With osimertinib alone, common causes include MET amplification and secondary EGFR mutations. In combination therapy, such as osimertinib plus chemotherapy, resistance can also involve small cell transformation. Newer combinations like amivantamab with lazertinib appear to significantly reduce resistance rates.
Monitoring ctDNA through liquid biopsy allows earlier detection of disease progression, often months before changes appear on imaging. Certain biomarkers, such as TP53 mutations or detectable EGFR mutations in blood at baseline, are linked to poorer responses and may signal the need for more aggressive initial treatment.
When first-line targeted therapies fail, newer options are emerging. These include bispecific antibodies like ivonescimab and antibody-drug conjugates such as sacituzumab tirumotecan, both showing improved outcomes over chemotherapy. Experts emphasize the importance of repeated tissue and liquid biopsies to guide more personalized second-line treatment strategies.