Ceritinib as a long-term disease control: Clinical observation

Abstract

ALK-positive non-small cell lung cancer is an excellent model demonstrating the success of precision medicine. A rare genetic disorder – a rearrangement of the anaplastic large cell lymphoma gene, occurring with a frequency of 5–7%, forms a certain clinical and morphological portrait of the patient. In ALK-positive non-small cell lung cancer, the brain is a frequent target for metastasis. But despite this negative prognosis factor, it is in this cohort of non-small cell lung cancer patients that the achievements of drug antitumor therapy are especially significant – the consistent use of ALK inhibitors of several generations allows to achieve a median overall survival of about 80 months. In the Russian Federation, 4 drugs have been approved for the treatment of ALK-positive non-small cell lung cancer. One of them is a second–generation ALK inhibitor – ceritinib is actively used both in the first line of therapy and after progression on crizotinib. In the ASCEND-4 registration study, the median time to progression on ceritinib was twice as long as on standard polychemotherapy. However, the initial daily dose of the drug 750 mg was associated with severe gastrointestinal and hepatotoxicity. Subsequently, the dose of the drug was reduced to 450 mg, which significantly improved the tolerability of treatment without reducing its effectiveness. The clinical case presented below demonstrates the possibility of modern targeted therapy to provide long-term disease control in metastatic ALK-positive nonsmall cell lung cancer.