Response to alectinib after one year of discontinuation of crizotinib in anaplastic lymphoma kinase-positive non-small-cell lung cancer: A case report

Abstract

Abstract. Therapy with crizotinib achieves prolonged progression-free and overall survival in non-small-cell lung cancer (NSCLC) patients with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK). It was demonstrated that ALK-positive NSCLCs exhibit a high response rate to the ALK inhibitor, crizotinib. However, a proportion of the patients discontinue crizotinib treatment due to adverse events. This is the case report of a NSCLC patient with EML4-ALK rearrangement, who, following crizotinib discontinuation for one year due to adverse events, exhibited a marked response to alectinib. Even if the incidence is not high, clinicians should not overlook the most common crizotinib-related adverse events. Furthermore, certain patients may continue to benefit from alectinib following long-term discontinuation of crizotinib therapy. IntroductionThe treatment of patients with advanced non-small-cell lung cancer (NSCLC) harboring echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase (EML4-ALK) rearrangement has been revolutionized by the development of crizotinib, a small-molecule inhibitor of the receptor tyrosine kinases ALK, ROS1 and MET (1,2). Crizotinib has been reported to be well tolerated; however, a proportion of the patients are unable to continue treatment due to the adverse events (2). Several more potent and highly selective second-generation ALK inhibitors have recently emerged for the treatment of ALK-positive NSCLC, such as alectinib (3). Alectinib appears to exhibit a more favorable toxicity profile compared to crizotinib (4). This is the case report of a NSCLC patient successfully treated with alectinib, following discontinuation of crizotinib therapy for one year due to adverse events. This case indicates that selected patients may continue to benefit from alectinib following long-term discontinuation of crizotinib therapy. Case reportA 41-year-old male patient presented with bilateral cervical and axillar lymph node enlargement. The patient underwent a chest computed tomography (CT) scan, which revealed a nodule in the right upper pulmonary lobe and ipsilateral mediastinal lymph node enlargement. A cervical node biopsy was performed and the histological examination confirmed the diagnosis of adenocarcinoma. Immunohistochemical staining was positive for thyroid transcription factor-1 and surfactant protein A. The patient had an Eastern Cooperative Oncology Group performance status of 1 and received 4 cycles of carboplatin, pemetrexed and bevacizumab. As the tumor response according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines was classified as partial response (PR), the patient subsequently received maintenance chemotherapy with pemetrexed and bevacizumab for 6 cycles. However, the treatment was discontinued due to disease progression.Written informed consent for the publication of the medical documents was obtained from the patient.As fluorescence in situ hybridization revealed a translocation of ALK, the patient receiv...