Sustained Clinical Response to 4th-Line Therapy with Selpercatinib in RET Fusion-Positive Combined Small Cell Lung Cancer

Abstract

Yan Huang,1,2,* Shuang Dai,1,2,* Wenlian Yin,3 Feng Luo,1,2 Yan Li2,4 1Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Lung Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Li, Department of Radiation Oncology, Cancer Center, West China Hospital, Sichuan University, No. 37, Guo Xue Xiang, Chengdu, Sichuan, 610041, People’s Republic of China, Email [email protected]: Combined small cell lung cancer (C-SCLC) is a relatively rare subtype of small cell lung cancer (SCLC) which combines SCLC and any component of non-small cell carcinoma (NSCLC). Patients diagnosed with C-SCLC are currently recommended to receive the same treatment as SCLC cases in the absence of clear evidence suggesting different strategies. The genomic profiling of C-SCLC is rarely studied. Herein, we report a case of extensive-stage C-SCLC harboring the KIF5B-RET fusion before first-line therapy and with persistent sensitivity to fourth-line selpercatinib treatment is reported.Materials and Methods: Molecular and pathological features were evaluated using transbronchial lung biopsy, immunohistochemical (IHC) staining and next-generation sequencing (NGS).Results: NGS revealed the KIF5B-RET fusion in the C-SCLC tumor. The patient had a progression-free survival (PFS) surpassing 14 months after selpercatinib treatment, with ongoing clinical response in 4th-line treatment.Conclusion: This case highlights the importance of comprehensive molecular testing in C-SCLC for selecting the optimal treatment. Although RET fusion is rare in patients with C-SCLC, its identification and treatment with selective RET inhibitors may contribute to clinical benefits.Keywords: combined small cell lung cancer, rearranged during transfection, selpercatinib, next-generation sequencing

Keywords

• combined small cell lung cancer
• rearranged during transfection
• selpercatinib
• next-generation sequencing