Journal Article

Mixed responses to first‐line alectinib in non‐small cell lung cancer patients with rare ALK gene fusions: A case series and literature review

Chen, Songan, Wang, Yina, Tang, Qiusu, Yan, Junrong, An, Zhou, Li, Mengnan, Ma, Yutong

2021

Overview

Anaplastic lymphoma kinase (ALK) fusion is a well‐defined biomarker for ALK tyrosine kinase inhibitors (TKIs) treatment in non‐small cell lung cancer (NSCLC). Alectinib, a second‐generation ALK‐TKI, has been shown to have significantly longer progression‐free survival (PFS) than first‐generation ALK inhibitors in untreated ALK‐rearranged NSCLC patients. However, its clinical efficacy on rare ALK fusions remains unclear. Herein, two advanced NSCLC patients received first‐line alectinib treatment, given their positive ALK fusion status as determined by immunohistochemistry (IHC) testing results. Patients showed limited clinical response (PFS: 4 months) and primary resistance to alectinib respectively. Molecular profiling using next‐generation sequencing (NGS) further revealed a striatin (STRN)‐ALK fusion in the first patient accompanied by MET amplification, and a LIM domain only protein 7 (LMO7)‐ALK fusion in another patient without any other known oncogenic alterations. Both patients demonstrated improved survival after they switched to second‐line crizotinib (PFS: 11 months) and ensartinib (PFS: 18 months), respectively, up till the last follow‐up assessment. In conclusion, the clinical efficacy of ALK‐TKIs including alectinib for lung cancer with uncommon ALK gene fusions is still under evaluation. This study and literature review results showed mixed responses to alectinib in NSCLC patients who harboured rare ALK fusions. Comprehensive molecular profiling of tumour is thus strongly warranted for precise treatment strategies.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Adult / alectinib / ALK protein / Anaplastic Lymphoma Kinase - genetics / Biomarkers, Tumor / c-Met protein / Carbazoles - administration & dosage / Carbazoles - adverse effects / Carbazoles - therapeutic use / Carcinoma, Non-Small-Cell Lung - diagnosis / Carcinoma, Non-Small-Cell Lung - drug therapy / Carcinoma, Non-Small-Cell Lung - genetics / Carcinoma, Non-Small-Cell Lung - mortality / Clinical trials / Disease Management / Female / Gene expression / Genetic Testing / Genomics / Histology / Humans / Immunohistochemistry / Inhibitor drugs / Kinases / Literature reviews / LMO7‐ALK / Lung cancer / Lung Neoplasms - diagnosis / Lung Neoplasms - drug therapy / Lung Neoplasms - genetics / Lung Neoplasms - mortality / Lymphatic system / Lymphoma / Male / Medical imaging / Metastasis / Middle Aged / Molecular Targeted Therapy / Neoplasm Staging / Non-small cell lung carcinoma / NSCLC / Oncogene Proteins, Fusion - genetics / Patients / Piperidines - administration & dosage / Piperidines - adverse effects / Piperidines - therapeutic use / Prognosis / Protein Kinase Inhibitors - administration & dosage / Protein Kinase Inhibitors - adverse effects / Protein Kinase Inhibitors - therapeutic use / Protein-tyrosine kinase / Proteins / rare ALK fusion / Short Communication / Small cell lung carcinoma / STRN‐ALK / survival / Thyroid cancer / Tomography / Tomography, X-Ray Computed / Treatment Outcome / Tumors