Reference Detail

Ref Type

Journal Article

PMID

(33380260)

Authors

Meng Z, Li T, Wang P, Lizaso A, Huang D

Title

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

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cancer biology & therapy	22	1	2021 01 02	1-4	Cancer Biol Ther

URL

Abstract Text

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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance
ALK	G1202L	missense	unknown	ALK G1202L lies within the protein kinase domain of the Alk protein (UniProt.org). G1202L has been identified in the scientific literature (PMID: 33380260), but has not been biochemically characterized and therefore, its effect on Alk protein function is unknown (PubMed, Apr 2024).

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
EML4 - ALK ALK G1202L	lung adenocarcinoma	predicted - sensitive	Lorlatinib	Case Reports/Case Series	Actionable	In a clinical case study, treatment with Lorbrena (lorlatinib) resulted in stable disease with a progression-free survival of 9 months in a patient with lung adenocarcinoma harboring EML4-ALK (e6:e20) and ALK G1202L, which was acquired after prior ALK inhibitor therapy (PMID: 33380260).	33380260