Transformation of ALK-positive NSCLC to SCLC after alectinib resistance and response to combined atezolizumab: a case report

BACKGROUND: The genotypic and histological evolution of non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC) has been described as a mechanism of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs). However, it was extremely rare in anaplastic lymphoma kinase (ALK) positive NSCLC, and the follow-up care and outcomes of patients with this rare condition were unclear. This case was the first described the effectiveness of combined chemo-immunotherapy in a patient, with a transformed ALK positive NSCLC into SCLC after the administration of an ALK-TKIs. CASE DESCRIPTION: We described a unique case in which a patient with ALK-positive NSCLC underwent SCLC transformation at a metastatic site and remained ALK positive after TKI treatment. In July 2019, a 77-year-old man was diagnosed with ALK-positive stage IVB NSCLC, received alectinib and responded to alectinib. It was not until more than 7 months later that a cranial MRI showed brain metastases. And whole-brain radiotherapy was administered, and secondary epilepsy and metastatic progression occurred. One year later, computed tomography showed a left submandibular mass with multiple lymph node metastases, a left lower lung mass, and right pleura thickening. A left submandibular biopsy revealed SCLC. Echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) fusion and low tumor mutation burden (2.23 muts/Mb) were identified by next generation sequencing. The patient was administered atezolizumab (1,200 mg, d1) in combination with etoposide (0.13 g, d1–d3) and carboplatin (350 mg, d1). The left neck mass was reduced significantly, showing a partial response. Serum NSE (from 106 to 15 ng/mL), CA19-9 (from 49.4 to 34.6 U/mL) and CEA (from 4.18 to 3.09 ng/mL) returned to normal. Only mild myelosuppression (Grade 1), fatigue (Grade 1), and anorexia (Grade 1) were present. The patient had an overall survival time of 21 months. CONCLUSIONS: This case highlighted the importance of re-biopsies to reveal pathological SCLC transformation after ALK-TKI resistance, and suggested the treatment of atezolizumab in combination with etoposide and carboplatin were potentially helpful for this phenotype.