PP01.69 Atypical Lung Carcinoids with EML4-ALK Fusion and Responses to ALK Inhibitors
Recommended Citation
Waliany S, Hung YP, Abu Rous F, Do A, Peterson J, Meservey C, Digumarthy SR, Gadgeel SM, Lin JJ, Meador CB. PP01.69 Atypical Lung Carcinoids with EML4-ALK Fusion and Responses to ALK Inhibitors. J Thorac Oncol 2024; 19:e32-e33.
Document Type
Conference Proceeding
Publication Date
7-1-2024
Publication Title
J Thorac Oncol
Abstract
Background: Genomic profiling (e.g., next-generation sequencing [NGS]) is not routinely performed for advanced lung carcinoids per current guidelines. However, targetable oncogenic fusions such as anaplastic lymphoma kinase (ALK) fusions can be identified in pulmonary neuroendocrine tumors. Data informing optimal management of these cases are limited. Methods: We report clinical outcomes and molecular profiling of two cases of ALK fusion-positive atypical lung carcinoid with responses to ALK tyrosine kinase inhibitors (TKIs). Results: Case 1: A 66-year-old female with nonsmoking history presented with dyspnea and cough. CT and PET revealed an FDG-avid mediastinal mass, azygoesophageal recess nodule, and adrenal nodule. Biopsies identified distinct histopathologies, consistent with adenosquamous carcinoma in the mediastinal mass and atypical carcinoid in the azygoesophageal recess. Immunohistochemistry (IHC) demonstrated ALK immunoreactivity (Figure), and NGS detected an EML4-ALK fusion at both disease sites. Lorlatinib was initiated with confirmed partial response (per RECIST v1.1), ongoing at 5 months. Case 2: A 58-year-old female with nonsmoking history presented with cough. Imaging revealed an FDG-avid mediastinal mass, pleural nodularity, and osseous lesions. Biopsies of the mediastinal mass and pleural nodule demonstrated atypical carcinoid. Tumor and liquid NGS testing detected EML4-ALK. Alectinib was initiated with tumor shrinkage (stable disease per RECIST v1.1), followed by progression at 5 months. Liquid biopsy NGS at the time of alectinib resistance revealed ALK G1202R and V1180L resistance mutations. Second-line lorlatinib achieved partial response for 7 months. Lorlatinib-resistant plasma NGS revealed multiple ALK mutations including G1202R, C1156Y, F1174L, and S1206F. Conclusions: Patients with ALK fusion-positive advanced atypical lung carcinoids can derive meaningful clinical benefit from ALK TKI therapy, highlighting the potential clinical value of genomic biomarker profiling in lung carcinoids with otherwise limited systemic therapy options. Further molecular analyses of Case 1 are underway and planned for inclusion at congress presentation. [Formula presented]
Volume
19
First Page
e32
Last Page
e33
