The efficacy of lorlatinib in a lung adenocarcinoma patient with a novel ALK G1202L mutation: a case report

Cancer Biol Ther. 2021 Jan 2;22(1):1-4. doi: 10.1080/15384047.2020.1836947. Epub 2020 Dec 30.


Acquired mutations in anaplastic lymphoma kinase (ALK) gene have been implicated as the major resistance mechanism to ALK inhibitors; however, information on the treatment options after acquiring novel ALK secondary mutations is limited. Herein, we report the efficacy of lorlatinib upon the detection of a novel ALK G1202L after progression on brigatinib. Our patient was a 30-year-old man with ALK-rearranged advanced lung adenocarcinoma. He had a partial clinical response to crizotinib lasting 11 months. Brigatinib was then administered for 12.8 months with stable disease as the best response. Sequencing at progression revealed the retention of EML4-ALK fusion and the emergence of a novel ALK G1202L mutation. With no standard treatment available, lorlatinib was administered, which achieved disease control for 9 months. Our report reveals the efficacy of lorlatinib in targeting ALK G1202L and can serve as an option for the clinical management of patients with ALK-rearranged lung adenocarcinoma after acquiring G1202L-mediated resistance from prior ALK inhibitor therapy. Furthermore, we also demonstrate the sequential use of crizotinib, brigatinib, and lorlatinib in a patient with advanced ALK-rearranged lung adenocarcinoma with an overall progression-free survival of 33.3 months for the sequential ALK inhibitor regimens. His overall survival was 41.5 months inclusive of all regimens.

Keywords: ALK G1202L; ALK inhibitor resistance; ALK-rearranged NSCLC; lorlatinib; sequential ALK inhibitors.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / drug therapy*
  • Adenocarcinoma of Lung / pathology
  • Adult
  • Aminopyridines / pharmacology
  • Aminopyridines / therapeutic use*
  • Anaplastic Lymphoma Kinase / metabolism*
  • Humans
  • Lactams / pharmacology
  • Lactams / therapeutic use*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / pathology
  • Male
  • Mutation
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use*


  • Aminopyridines
  • Lactams
  • Pyrazoles
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • lorlatinib

Grants and funding

This work was supported by National Natural Science Foundation of China [grant number 81572321 to DH] and the Wu Jieping Medical Foundation [grant number 320.6750.18158 to ZM].