Abstract
RATIONALE: SMARCA4-deficient non-small cell lung cancer (NSCLC) represents a highly aggressive subtype with poor prognosis. While clinical studies have identified common co-mutations in TP53, LRP1B, STK11, KEAP1, and KRAS, actionable driver mutations such as EGFR or ALK are rarely reported in conjunction with SMARCA4 deficiency. This case presents a rare instance of NSCLC featuring both an EGFR exon 21 L858R mutation and SMARCA4 deficiency, highlighting the challenges in treatment and the need for novel therapeutic strategies. PATIENT CONCERNS: A 79-year-old female patient presented with concerns of a lung mass, suspected to be peripheral lung cancer based on diagnostic imaging. DIAGNOSES: Histopathological evaluation confirmed SMARCA4-deficient NSCLC. Molecular genetic analysis further revealed an EGFR exon 21 L858R mutation. INTERVENTIONS: The patient was initially treated with osimertinib, an EGFR tyrosine kinase inhibitor. Upon disease progression, treatment was adjusted to include anlotinib in combination with ongoing osimertinib. OUTCOMES: The initial treatment with osimertinib led to partial remission. However, disease progression necessitated a change in therapy. The combination treatment stabilized the disease temporarily, achieving a stable disease status. LESSONS: This case underscores the transient efficacy of targeted therapy in SMARCA4-deficient NSCLC with concurrent EGFR mutations. It highlights the need for continuous therapeutic adjustments and emphasizes the importance of further research into effective strategies for treating this complex and challenging subset of NSCLC, as current modalities have limitations in sustained efficacy.