Abstract
BACKGROUND: The emergence of the epidermal growth factor receptor (EGFR) C797S mutation in the absence of T790M represents a common mechanism of acquired resistance to first-line osimertinib in non-small cell lung cancer (NSCLC), posing a significant clinical challenge. CASE PRESENTATION: We present the case of a 72-year-old man diagnosed with metastatic NSCLC harboring an EGFR exon 19 deletion who developed an acquired C797S mutation (without T790M) following 25 months of first-line osimertinib therapy. Based on this molecular profile, the patient received a regimen of gefitinib combined with bevacizumab. This combination was well tolerated and resulted in a partial response, achieving a progression-free survival (PFS) of 15.5 months. CONCLUSION: This case indicates that the combination of gefitinib and bevacizumab may offer a durable clinical benefit for NSCLC patients who develop osimertinib resistance via the C797S mutation. The observed outcomes warrant further investigation into this dual-blockade strategy, especially given the limited duration of response noted for tyrosine kinase inhibitor (TKI) monotherapy.