Transformation to neuroendocrine carcinoma as a resistance mechanism to lorlatinib

Niamh Coleman; Andrew Wotherspoon; Nadia Yousaf; Sanjay Popat

doi:10.1016/j.lungcan.2019.05.025

Transformation to neuroendocrine carcinoma as a resistance mechanism to lorlatinib

Lung Cancer. 2019 Aug:134:117-120. doi: 10.1016/j.lungcan.2019.05.025. Epub 2019 Jun 6.

Authors

Niamh Coleman¹, Andrew Wotherspoon², Nadia Yousaf³, Sanjay Popat⁴

Affiliations

¹ Lung Unit, The Royal Marsden Hospital, 203 Fulham Rd, Chelsea, London, SW3 6JJ, United Kingdom. Electronic address: [email protected].
² Department of Histopathology, The Royal Marsden Hospital, 203 Fulham Rd, Chelsea, London, SW3 6JJ, United Kingdom.
³ Lung Unit, The Royal Marsden Hospital, 203 Fulham Rd, Chelsea, London, SW3 6JJ, United Kingdom.
⁴ Lung Unit, The Royal Marsden Hospital, 203 Fulham Rd, Chelsea, London, SW3 6JJ, United Kingdom. Electronic address: [email protected].

PMID: 31319969
DOI: 10.1016/j.lungcan.2019.05.025

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.

Keywords: ALK positive; NSCLC; Neuroendocrine transformation; Oncogene addicted; Small cell lung cancer.

Publication types

Case Reports

MeSH terms

Adult
Aminopyridines
Anaplastic Lymphoma Kinase / genetics
Antineoplastic Agents / pharmacology*
Antineoplastic Agents / therapeutic use
Antineoplastic Combined Chemotherapy Protocols / adverse effects
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Carcinoma, Neuroendocrine / diagnosis*
Carcinoma, Neuroendocrine / drug therapy
Carcinoma, Neuroendocrine / genetics
Cell Line, Tumor
Cell Transformation, Neoplastic* / genetics
Drug Resistance, Neoplasm* / genetics
ErbB Receptors / genetics
Gene Rearrangement
Humans
Lactams
Lactams, Macrocyclic / pharmacology*
Lactams, Macrocyclic / therapeutic use
Liver Neoplasms / diagnosis
Liver Neoplasms / secondary
Lung Neoplasms / diagnosis
Lung Neoplasms / genetics
Lung Neoplasms / therapy
Male
Molecular Targeted Therapy
Mutation
Neoplasm Metastasis
Neoplasm Staging
Pyrazoles
Tomography, X-Ray Computed

Substances

Aminopyridines
Antineoplastic Agents
Lactams
Lactams, Macrocyclic
Pyrazoles
ALK protein, human
Anaplastic Lymphoma Kinase
EGFR protein, human
ErbB Receptors
lorlatinib