Small-cell transformation is a clinically resistant mechanism against epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in lung adenocarcinoma (LUAD). It often leads to poor outcomes and limited treatment options. This case report describes an advanced case of LUAD with an EGFR exon 19 deletion and a BRCA2 mutation. After failing several therapies, the disease progressed to a histologically confirmed small-cell lung cancer (SCLC) phenotype. In this case, treatment with olaparib (150 mg/day), combined with temozolomide (50 mg/day) and atezolizumab for two cycles, resulted in a partial tumor response. The patient experienced grade IV myelosuppression, consistent with a previous episode of severe haematologic toxicity during chemotherapy. This case highlights the potential value of combining olaparib, temozolomide, and immune checkpoint inhibition as a therapeutic strategy for BRCA2 -mutated small-cell transformation arising from LUAD. However, significant haematologic adverse effects require careful monitoring.
Liu et al. (2026) studied this question.