Related Experiment Video
Updated: Jul 14, 2026
Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
Complete Response to Lorlatinib in Lung Adenocarcinoma With EML4-ALK Fusion Variant (E6;A18): Case Report and
Antonio Vitale1,2, Elisa De Paolis3, Jacopo Russo1,2
11Medical Oncology Department, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Abstract:
ALK gene rearrangements represent a targetable driver in non-small cell lung cancer (NSCLC), but rare fusion variants remain poorly characterized and their sensitivity to ALK inhibitors is uncertain. This report describes a 67-year-old woman with stage IV lung adenocarcinoma in whom comprehensive genomic profiling (CGP) identified a rare EML4-ALK (E6;A18) fusion, subsequently confirmed by immunohistochemistry (IHC). Following first-line therapy with lorlatinib, the patient demonstrated rapid clinical improvement, radiologic tumor regression, and a complete metabolic response, including resolution of central nervous system metastases. No significant adverse effects were observed during treatment. This case provides the first evidence of complete and durable response with lorlatinib in a patient with NSCLC harboring the rare EML4-ALK (E6;A18) fusion. This report underscores the importance of integrating CGP with IHC for accurate molecular diagnosis and therapeutic decision-making in the context of atypical ALK fusions. It also highlights the clinical activity of next-generation ALK inhibitors against uncommon fusion variants, suggesting that even structurally distinct fusions may be sensitive to targeted therapy. Further research is warranted to validate treatment strategies in these rare genomic contexts.
Insights
A rare EML4-ALK (E6;A18) fusion in non-small cell lung cancer (NSCLC) responded durably to lorlatinib. This case highlights the efficacy of next-generation inhibitors against uncommon ALK fusion variants.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- ALK gene rearrangements are key drivers in non-small cell lung cancer (NSCLC).
- Rare ALK fusion variants present diagnostic and therapeutic challenges due to limited characterization.
- Sensitivity of uncommon ALK fusions to ALK inhibitors remains uncertain.
Purpose of the Study:
- To report the first evidence of a durable response to lorlatinib in NSCLC with a rare EML4-ALK (E6;A18) fusion.
- To underscore the importance of comprehensive genomic profiling (CGP) and immunohistochemistry (IHC) for diagnosing atypical ALK fusions.
- To highlight the clinical activity of next-generation ALK inhibitors against uncommon fusion variants.
Main Methods:
- Comprehensive genomic profiling (CGP) identified a rare EML4-ALK (E6;A18) fusion in a patient with stage IV lung adenocarcinoma.
- Immunohistochemistry (IHC) confirmed the EML4-ALK (E6;A18) fusion.
- Treatment with first-line lorlatinib was administered.
Main Results:
- The patient achieved rapid clinical improvement, radiologic tumor regression, and a complete metabolic response.
- Central nervous system metastases resolved completely.
- No significant adverse effects were observed during lorlatinib treatment.
Conclusions:
- Lorlatinib demonstrated complete and durable efficacy in a patient with NSCLC harboring the rare EML4-ALK (E6;A18) fusion.
- Integrated CGP and IHC are crucial for accurate molecular diagnosis and treatment decisions in atypical ALK fusions.
- Next-generation ALK inhibitors show promise against structurally distinct, uncommon fusion variants, warranting further research.
More Related Videos
09:49Oncogenic Gene Fusion Detection Using Anchored Multiplex Polymerase Chain Reaction Followed by Next Generation Sequencing
Published on: July 5, 2019
07:59Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
