Stage IVA EGFR-mutant lung adenocarcinoma: response to triple targeted therapy and surgery

What happened, in summary

This 56-year-old Chinese woman, a never-smoker, developed 1 month of cough and chest pain. CT showed a 4.3 cm left upper-lobe lung mass, mediastinal and left hilar lymphadenopathy, multiple left-lung nodules, and left pleural thickening with effusion. PET-CT showed no metastases outside the chest, but the pleural and pulmonary disease made this Stage IVA lung adenocarcinoma, cT4N2M1a. Biopsy confirmed lung adenocarcinoma, and molecular testing found an EGFR exon 19 deletion. She started osimertinib 80 mg once daily on 13 November 2023. After 3 months, the main left upper-lobe lesion had partially responded, and pleural disease and lymph nodes had regressed, but a left lower-lobe dorsal lesion progressed. Biopsy of that progressing lesion again showed adenocarcinoma. NGS found the original EGFR exon 19 deletion plus a new BRAF V600E mutation, consistent with acquired resistance. On 19 February 2024, she began triple targeted therapy with osimertinib, dabrafenib, and trametinib. Four months later, imaging showed the left upper-lobe lesion remained stable and the left lower-lobe lesion had markedly regressed; the only reported side effect was grade 1 rash. In June 2024, she underwent left upper-lobe lingula segmentectomy, left lower-lobe dorsal segmentectomy, and systematic lymphadenectomy. Pathology showed only 1% viable tumor in both lung lesions and complete pathologic response in 7 lymph nodes. As of May 2025, she continued triple therapy with no progression. Her course shows how repeat biopsy at progression can identify a new resistance driver and guide a tailored combination strategy, while surgery can provide pathologic confirmation of how much viable cancer remains after systemic targeted therapy.