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Alectinib/ceritinib Acquired resistance and nephrotoxicity: case report

A 51-year-old man developed acquired resistance and nephrotoxicity during treatment with alectinib and ceritinib, respectively for ALK-positive lung cancer [routes and outcomes not stated]. The man, who had no history of prior malignancies, radiation or chemotherapy, was hospitalised in the coronary care unit because of acute heart failure and pericardial effusion. He was an ex-smoker. Subsequently, he was diagnosed with ALK-positive lung cancer and started receiving treatment with alectinib 600 mg/day. Alectinib inhibited lung tumour growth, and he was discharged 20 days following alectinib administration. However, 3 months later, metastatic liver tumours quickly regrew. It was considered that he acquired resistance to alectinib therapy. Subsequently, the man was administered 4 cycles of cisplatin 75 mg/m2 plus pemetrexed 500 mg/m2, followed by 2 cycles of maintenance therapy with pemetrexed. However, his disease progressed. Later, he was administered ceritinib 750 mg/day, but it showed little effect on tumour growth. On day 15 of ceritinib administration, the drug was discontinued due to grade 2 nephrotoxicity. It was restarted on day 19, but he again developed grade 2 nephrotoxicity, and ceritinib was discontinued again on day 28. On day 31, he developed grade 3 anorexia and disease progression, and the drug was eventually withdrawn. He was then administered crizotinib 500 mg/day, leading to slight reductions in the pleural effusion but lymphangitic carcinomatosis of the right lung, although progression of multiple liver metastases was noted. The small brain metastases observed in the parietal lobe and temporal lobe at diagnosis ameliorated after 1.5 months of alectinib treatment. Before the initiation of ceritinib, the metastases regrew; however, following ceritinib therapy, these lesions were not clear in the brain MRI. He survived with lung cancer for only 12 months [immediate cause of death not stated]. An autopsy was performed after his family consent. Makimoto G, et al. Rapid Acquisition of Alectinib Resistance in ALK-Positive Lung Cancer With High Tumor Mutation Burden. Journal of Thoracic Oncology 14: 2009-2018, No. 11, Nov 2019. Available from: URL: http://doi.org/10.1016/j.jtho.2019.07.017

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Editorial comment: Details of this case report have previously been published and processed for Adis PV [see Reactions 1680 p21; 803284842].

0114-9954/20/1822-0001/$14.95 Adis © 2020 Springer Nature Switzerland AG. All rights reserved

Reactions 19 Sep 2020 No. 1822