2022 World Conference on Lung Cancer (ePosters)-EP08.02-037. Small Cell Transformation in a Patient with RET Fusion Positive Lung Adenocarcinoma on Pralsetinib

EP08.02-037. Small Cell Transformation in a Patient with RET Fusion Positive Lung Adenocarcinoma on Pralsetinib

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This case report discusses the development of small cell lung cancer in a patient with RET fusion positive lung adenocarcinoma who was being treated with pralsetinib, a RET tyrosine kinase inhibitor. RET fusions are found in about 1-2% of non-small cell lung cancers, and these tumors typically respond to RET inhibitors. However, secondary resistance to these inhibitors is common. In this case, the patient initially responded to pralsetinib treatment, but after three months, there was evidence of disease progression in the subcarinal lymph node. The patient underwent bronchoscopy and debulking, followed by concurrent chemotherapy and radiation. Pralsetinib treatment was then resumed, but after two more months, there was further progression of the disease, with the formation of a fistula between the left mainstem bronchus and the subcarinal lymph node. Biopsy revealed the transformation of the adenocarcinoma into small cell lung cancer, which tested positive for synaptophysin, CD56, INSM1, and ASCL1, and negative for TTF-1 and Napsin A, suggesting a distinct immunoprofile compared to the initial adenocarcinoma. The patient eventually enrolled in hospice care and passed away 8 months after diagnosis. Molecular analysis of the small cell carcinoma biopsy revealed the retention of the KIF5B::RET fusion, MYC amplification, and a TP53 mutation. This case represents the first reported instance of resistance to a RET inhibitor through transformation into small cell carcinoma. The presence of the TP53 mutation may have contributed to this transformation.

Asset Subtitle

Anastasios Dimou

Meta Tag

Speaker Anastasios Dimou

Topic Metastatic Non-small Cell Lung Cancer - Molecular Targeted Treatments

Keywords

small cell lung cancer

RET fusion positive lung adenocarcinoma

pralsetinib

RET tyrosine kinase inhibitor

non-small cell lung cancers

RET inhibitors

secondary resistance

subcarinal lymph node

bronchoscopy and debulking

concurrent chemotherapy and radiation