Non small cell lung cancer with SMARCA4 deficiency harboring rare EGFR mutations exhibited significant tumor response when treated with afatinib: a case report

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