Transformation to neuroendocrine carcinoma as a resistance mechanism to lorlatinib. (August 2019)

• Record Type: Journal Article
• Authors: Coleman, Niamh; Wotherspoon, Andrew; Yousaf, Nadia; Popat, Sanjay
• Is Part Of: Lung cancer. Volume 134(2019)
• Page Start: 117
• Page End: 120
• Publication Date: 2019-08
• Subjects: NSCLC -- ALK positive -- Oncogene addicted -- Neuroendocrine transformation -- Small cell lung cancer; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2019.05.025
• Languages: English
• ISSNs: 0169-5002

Abstract

Graphical abstract: Highlights: Small cell transformation is a poorly-described phenomenon in ALK-rearranged NSCLC. We report transformation to a neuroendocrine carcinoma as an acquired resistance mechanism to lorlatinib. Acquisition of gatekeeper ALK 1196 M mutation is also noted. We highlight that, if feasible, re-biopsy on progression should be standard of care over liquid biopsy. Abstract: Objectives: Small cell transformation is a well-recognized mechanism of resistance to EGFR-TKI therapy in EGFR-mutant NSCLC, yet it remains a poorly-described phenomenon in ALK-rearranged NSCLC. Material and methods: Chart and literature review. Results: We report a case of a patient with ALK-rearranged lung cancer progressing on three-lines of ALK-targeted therapies, with development of acquired resistance to lorlatinib, with both transformation to a neuroendocrine carcinoma, and acquisition of ALK 1196 M. Conclusions: Given the inevitable development of resistance in ALK + NSCLC, if feasible, re-biopsy on progression should be standard over liquid biopsy. Neuroendocrine carcinoma transformation remains an important mechanism of acquired resistance to lorlatinib.