Remarkable Clinical Response of ALK-Rearranged/TP53-Mutant Lung Adenocarcinoma with Liver Metastasis to Atezolizumab-Bevacizumab-Carboplatin-Paclitaxel After ALK Inhibitors: A Case Report

Hirokazu Iso,1 Akihiko Miyanaga,1 Naohiro Kadoma,1 Kaoruko Shinbu,1 Takehiro Tozuka,1 Akari Murata,1 Shunichi Nishima,1 Yozo Sato,1 Shinji Nakamichi,1 Masaru Matsumoto,1 Rintaro Noro,1 Yasuhiro Terasaki,2 Kaoru Kubota,1 Masahiro Seike1 1Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan; 2Department of Analytic Human Pathology, Nippon Medical School, Tokyo, JapanCorrespondence: Akihiko Miyanaga, Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo, 113-8603, Japan, Tel +81 3 3822 2131, Fax +81 3 5685 3075, Email a-miyanaga@nms.ac.jpAbstract: Anaplastic lymphoma kinase-positive (ALK-positive) lung adenocarcinoma with multiple liver metastases accounts for a relatively small number of cases of non-small cell lung cancer. Several ALK-tyrosine kinase inhibitors (ALK-TKIs) are available for the treatment of lung cancer. However, there is limited evidence on the treatment of multiple liver metastases in patients with lung cancer that are refractory to ALK-TKIs. We report the case of a 42-year-old male patient with ALK-positive lung adenocarcinoma who experienced rapid progression to multiple liver metastases while receiving treatment with alectinib. Biopsy of the liver metastases revealed echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) fusion and tumor protein p53 (TP53) mutation; notably, ALK secondary mutations were not detected. Despite the sequential administration of third-generation ALK-TKIs, the liver metastases did not respond, the serum levels of total bilirubin and biliary enzymes continued to increase, and the patient’s general appearance worsened. Finally, the patient exhibited a remarkable clinical response to treatment with a combination of atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP). ABCP is one of the optimal options for ALK-positive lung cancer with liver metastasis that is refractory