Lung cancers with SMARCA4 deficiency are rare, typically showing aggressive behaviour and poor prognosis.

These tumours rarely harbour 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 tumour response with afatinib.

A 53-year-old nonsmoking female patient presented with a one-month history of hoarseness.

Physical examination revealed dyspnoea 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 tumour.

The tumour 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 tumour 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 tumour 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 characterised by aggressive behaviour 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 tumour 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 tumour type.

Journal: Frontiers of Medicine

Source: Higher Education Press