OncoTargets and Therapy (Dec 2021)
Clinical Impact of Switching to Ceritinib After Severe AEs Related to Crizotinib/Alectinib in a Novel PTH2R-ALK Fusion Lung Adenocarcinoma: A Case Report
Abstract
Gang Shen,1,* Yinping Du,1,* Jifang Shen,1 Junling Zhang,2 Xihua Xia,2 Mengli Huang,2 Wenxiang Shen3 1Department of Radiology, The Affiliated Kunshan Hospital of Jiangsu University, Kunshan, People’s Republic of China; 2The Medical Department, 3D Medicines, Inc., Shanghai, People’s Republic of China; 3Department of Oncology, The Affiliated Kunshan Hospital of Jiangsu University, Kunshan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenxiang ShenDepartment of Oncology, The Affiliated Kunshan Hospital of Jiangsu University, 91 West Qianjin Road, Kunshan, Jiangsu Province, 215300, People’s Republic of ChinaEmail [email protected]: Lung cancer is still the leading cause of morbidity and mortality by cancer among men, according to the latest epidemiological data in China. Anaplastic lymphoma kinase (ALK) rearrangements act as key oncogenic drivers of non-small cell lung cancer (NSCLC) and have been identified in 5– 6% of NSCLC. Although ALK inhibitors (ALK-TKIs) were proven to be more effective than chemotherapy in ALK-positive NSCLC patients and the safety profile of these drugs was favorable, novel ALK fusions NSCLC might discontinue or switch treatment because of adverse events (AEs) have rarely previously been reported. Here, we describe a male patient with stage IV lung adenocarcinoma who carried a novel PTH2R-ALK fusion identified by next-generation sequencing (NGS). The patient first took crizotinib but switched to alectinib due to gastrointestinal AEs. Although alectinib remained effective on tumors, ceritinib (450 mg) was replaced after the AEs of hyperbilirubinemia occurred. After reducing the dose to 300mg, the diarrhea AEs caused by ceritinib were effectively relieved, and the patient obtained sustained clinical benefit with progression-free survival nearly 12 months. Our findings offer valuable information for the safety management of NSCLC patients with a novel PTH2R-ALK fusion treated by ALK-TKIs.Keywords: PTH2R-ALK, non-small cell lung cancer, ceritinib, adverse events
