Stage 4 lung cancer: 2-year survival with immunotherapy

What happened, in summary

This 53-year-old man came to Anhui Chest Hospital in July 2022 with persistent dull pain in the left chest. He had chronic non-atrophic gastritis but no smoking or alcohol history and no known family cancer predisposition. Chest CT showed a large left upper-lobe lung mass measuring about 6.2 cm by 5.4 cm, multiple small nodules in both lungs, left pleural effusion, and enlarged lymph nodes in the left hilum, supraclavicular area, and mediastinum. Pleural fluid cytology showed atypical cells, and lung biopsy confirmed SMARCA4-deficient lung adenocarcinoma. Immunohistochemistry showed CK, CK7, TTF-1, and partial napsin A positivity, Ki-67 about 50%, and loss of BRG1, supporting SMARCA4 deficiency. PD-L1 TPS was high at 90%. Brain MRI, bone scan, and abdominal/pelvic CT did not show additional metastases. Tumor sequencing found a MET exon 14 D1010H mutation, plus BRCA1, MSH6, and CDK12 alterations. EGFR, ALK, ROS1, KRAS, RET, STK11, and TP53 were not detected, and no tumor microsatellite instability was found. The final diagnosis was Stage IVa SMARCA4-deficient NSCLC with MET exon 14 alteration. Because of financial concerns and reluctance to receive chemotherapy, he declined MET inhibitor-targeted therapy and chemotherapy. Instead, he received sintilimab 200 mg on day 1 plus anlotinib 12 mg on days 1-14. After 2 cycles, CT showed marked shrinkage. By cycle 22, the primary lesion reached its deepest response, and by cycle 32, control was sustained. He remained progression-free for more than 2 years, with manageable rash, hypertension, angina, and hypothyroidism. Cardiac symptoms were also treated with coronary angioplasty after unstable angina developed during follow-up.