Lung cancers with SMARCA4 deficiency are rare, typically showing aggressive behavior and poor prognosis. These tumors rarely harbor common targetable oncogenes like EGFR, ALK, or ROS1. This case report details a nonsmoking middle-aged woman with SMARCA4-deficient non-small cell lung cancer (NSCLC) and rare EGFR mutations who achieved significant tumor response with afatinib.
A 53-year-old nonsmoking female patient presented with a one-month history of hoarseness. Physical examination revealed dyspnea and multiple enlarged lymph nodes in the supraclavicular, submandibular, and axillary regions. Imaging showed a right thoracic mass with irregular borders and dense shadows. Positron emission tomography/CT imaging revealed a heterogeneous increase in fluorodeoxyglucose metabolism in a soft tissue mass in the right lower pulmonary lobe, with multifocal lymph node metastases and a left parietal lobe cerebral metastatic tumor. The tumor was classified as cT2bN3M1c, stage IVB. Immunohistochemistry showed the absence of BRG1 and SALL4 and the positive expression of CK5/6 and CK7, confirming SMARCA4-deficient NSCLC. Genetic testing identified mutations in EGFR exon 20 S768I and exon 18 G719X.
The patient commenced targeted therapy with afatinib at a dose of 40 mg once daily. After one month, imaging revealed significant reduction in the primary tumor and metastatic lesions. A subsequent chest CT after three months of treatment confirmed remarkable response, with complete resolution of brain metastases. The patient achieved a progression-free survival of 17 months. Upon tumor progression, a repeat biopsy confirmed persistent SMARCA4 poorly differentiated carcinoma without T790M mutations. The patient opted for palliative care and passed away one month later.
SMARCA4-deficient NSCLC is characterized by aggressive behavior and resistance to conventional therapies. This case highlights the potential efficacy of afatinib in SMARCA4-deficient NSCLC with rare EGFR mutations. The patient's significant tumor response and prolonged progression-free survival suggest that targeted therapy should be considered for such cases. Further research is needed to understand the mechanisms underlying the coexistence of EGFR mutations with SMARCA4-deficient NSCLC and to develop optimal therapeutic strategies for this rare and aggressive tumor type.
DOI: 10.1007/s11684-024-1118-y
Frontiers of Medicine
Case study
People
Non small cell lung cancer with SMARCA4 deficiency harboring rare EGFR mutations exhibited significant tumor response when treated with afatinib: a case report
24-Feb-2025