Abstract
The second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) alectinib and ceritinib are standard treatment options for patients with non–small cell lung cancer (NSCLC) positive for ALK fusion genes. However, almost all patients eventually develop resistance to these drugs. We here report a case of ALK-rearranged NSCLC that developed resistance to alectinib but remained sensitive to ceritinib. The L1196M mutation within the ALK fusion gene was detected after failure of consecutive treatment with crizotinib and alectinib, but no other mechanism underlying acquired resistance to ALK-TKIs was found to be operative. Given the increasing application of ALK-TKIs to the treatment of patients with ALK-rearranged NSCLC, further clinical evaluation is warranted to provide a better understanding of the mechanisms of acquired resistance to these agents and to inform treatment strategies for such tumors harboring secondary mutations.
Highlights
Rearrangements of the anaplastic lymphoma kinase (ALK) gene have been detected in 3% to 7% of non–small cell lung cancers (NSCLCs) [1, 2]
We here report a case of ALK-rearranged NSCLC that progressed after treatment with crizotinib and www.oncotarget.com alectinib possibly due to L1196M secondary mutation, and subsequently manifested tumor shrinkage during treatment with ceritinib
We here describe a case of ALK-rearranged NSCLC that underwent disease progression during alectinib treatment, was found to harbor the L1196M mutation of ALK, and showed a response to ceritinib treatment
Summary
Rearrangements of the anaplastic lymphoma kinase (ALK) gene have been detected in 3% to 7% of non–small cell lung cancers (NSCLCs) [1, 2]. Alectinib shows pronounced anticancer activity against ALK fusion–positive NSCLC cells that harbor the most common crizotinib resistance mutations [3, 4] It reduced the risk of disease progression or death by 66% compared with crizotinib in a randomized phase III trial for ALK-TKI–naïve patients with ALK-rearranged NSCLC [5, 6]. The patient experienced disease recurrence as lung metastases She was treated with 3 cycles of bevacizumab plus carboplatin and paclitaxel as a first-line drug treatment, following 22 cycles of bevacizumab and pemetrexed as the maintenance therapy, but 2 years later computed tomography (CT) again revealed progression of her pulmonary disease. After 30 weeks of ceritinib administration, CT showed that the lung metastases had again progressed (Figure 2C) and brain magnetic resonance imaging revealed brain metastasis
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