Real-world therapeutic effectiveness of lorlatinib after alectinib in Japanese patients with ALK-positive non-small-cell lung cancer

Cancer Sci. 2023 Jun;114(6):2560-2568. doi: 10.1111/cas.15777. Epub 2023 Apr 2.


Alectinib, an anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), is the recommended first-line treatment for ALK-positive non-small-cell lung cancer (NSCLC) in Japan. Lorlatinib was approved as a subsequent therapeutic option after progression while receiving ALK TKI treatment. However, data on the use of lorlatinib in the second- or third-line setting after alectinib failure are limited in Japanese patients. This retrospective real-world observational study investigated the clinical effectiveness of lorlatinib in second- or later-line settings after alectinib failure in Japanese patients. Clinical and demographic data collected in the Japan Medical Data Vision (MDV) database between December 2015 and March 2021 were used. Patients diagnosed with lung cancer who received lorlatinib following alectinib failure after the November 2018 marketing approval of lorlatinib in Japan were included. Of 1954 patients treated with alectinib, 221 were identified from the MDV database as receiving lorlatinib after November 2018. The median age of these patients was 62 years. Second-line lorlatinib treatment was reported for 154 patients (70%); third- or later-line lorlatinib treatment was reported for 67 patients (30%). The median duration of treatment (DOT) for all lorlatinib-treated patients was 161 days (95% confidence interval [CI], 126-248), and 83 patients (37.6%) continued treatment after data cut-off (March 31, 2021). Median DOTs of 147 days (95% CI, 113-242) and 244 days (95% CI, 109 to not reached) were reported with second-line and third- or later-line treatment, respectively. Consistent with clinical trial data, this real-world observational study supports data suggesting the effectiveness of lorlatinib after alectinib failure in Japanese patients.

Keywords: Japan; anaplastic lymphoma kinase; carcinoma; lorlatinib; non-small-cell lung cancer; real-world clinical trials.

Publication types

  • Observational Study

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Antineoplastic Agents* / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • East Asian People
  • Humans
  • Lactams, Macrocyclic / therapeutic use
  • Lung Neoplasms* / pathology
  • Middle Aged
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Tyrosine Kinases
  • Retrospective Studies


  • lorlatinib
  • alectinib
  • Antineoplastic Agents
  • Anaplastic Lymphoma Kinase
  • Lactams, Macrocyclic
  • Protein-Tyrosine Kinases
  • Protein Kinase Inhibitors

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