EGFR-mutant lung adenocarcinoma with acquired ROS1 rearrangement after EGFR-TKI resistance

What happened, in summary

This 57-year-old woman, a never-smoker, was admitted in September 2016 with cough, sputum, and hemoptysis. She underwent thoracoscopic right lower lobectomy with mediastinal lymph-node dissection, and pathology confirmed invasive lung adenocarcinoma, pT2aN0M0, Stage IB. She received 1 cycle of adjuvant pemetrexed plus cisplatin, but treatment was stopped because of severe gastrointestinal toxicity. In August 2017, pain and limited movement in her left lower limb led to a bone scan showing distal femur metastasis. She received conformal radiotherapy to the femur, 40 Gy in 20 fractions, with pain relief, followed by bone-directed therapy including zoledronic acid, incadronate, and denosumab at different points. Molecular testing in December 2017 found an EGFR exon 19 deletion, and she started icotinib. As disease evolved, imaging showed progression in the distal femur, new left-lung metastases, pleural effusion, and later right-sided pulmonary embolism with massive pleural effusion. Repeat testing in April 2021 found acquired EGFR T790M, and she began befotertinib, with stable disease at 31 months. She later received intrapleural low-dose cisplatin plus endostatin for pleural symptoms and then anlotinib. In October 2023, enlarging left inguinal nodes with skin thickening were biopsied and confirmed metastatic lung adenocarcinoma. New testing found an acquired EZR exon10-ROS1 exon34 rearrangement, a rare resistance mechanism after EGFR-targeted therapy. The result shifted treatment toward ROS1 inhibition rather than continuing only EGFR-directed therapy. Crizotinib began in November 2023. By August 27, 2025, imaging showed partial response, and a September 2025 bone scan showed stable lesions. The only reported adverse event was moderate lower-limb edema, with no intolerable side effects.