ALK-rearranged lung adenocarcinoma patient with development of severe sinus bradycardia after treatment with crizotinib: A case report

RATIONALE: The anaplastic lymphoma kinase (ALK) rearrangements represent a subtype of nonsmall-cell lung cancer (NSCLC), and targeting ALK has radically changed the treatment of NSCLC. Crizotinib, as an ALK inhibitor, has been used in the treatment of ALK-rearranged NSCLC for several years and some adverse effects should be given attention. PATIENT CONCERNS: A 64-year-old woman with a no-smoking history visited hospital in November 2016 because of a persistent cough, expectoration, and progressive dysphagia for 2 months. DIAGNOSES AND INTERVENTIONS: She was diagnosed with primary lung adenocarcinoma, accompanied by pleural and bone metastases. After receiving chemotherapy for nearly 1 year, she showed progressive disease. DNA-sequencing identified an intergenic ALK rearrangement. Surprisingly, RNA-sequencing revealed the EML4-ALK fusion transcript. Subsequently, this patient switched to crizotinib therapy. OUTCOMES: The patient achieved partial response after 1-month treatment. However, this patient suffered a severe sinus bradycardia after 4 months of treatment. When reducing the dose of crizotinib, the side effect was alleviated and this patient showed stable disease until now. LESSONS: Given that the severe sinus bradycardia was an unusual adverse effect, physicians should be aware of these side effects when using crizotinib. Moreover, it should be noted that this patient harbored an intergenic ALK rearrangement identified by DNA-sequencing, but EML4-ALK fusion transcript verified by RNA-sequencing. However, the mechanism remains unknown and requires further research.