Combined RET and MEK Inhibition as a Treatment for RET Fusion-Positive NSCLC With Acquired BRAF Fusion: A Case Report

Jacobi B. Hines; Benjamin C. Bowar; Margaret Colleton; Lydia Chelala; Peng Wang; Angad A. Chadha; Jeremy Segal; Christine M. Bestvina

doi:10.1016/j.jtocrr.2024.100724

Combined RET and MEK Inhibition as a Treatment for RET Fusion-Positive NSCLC With Acquired BRAF Fusion: A Case Report

Jacobi B. Hines, Benjamin C. Bowar, Margaret Colleton, Lydia Chelala, Peng Wang, Angad A. Chadha, Jeremy Segal, Christine M. Bestvina^*

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

Abstract

RET fusions are present in 1% to 2% of NSCLCs. Although RET inhibitors like selpercatinib are effective, resistance inevitably develops. We present the case of a 28-year-old female with recurrent NSCLC and a CCDC6::RET fusion treated with selpercatinib. Testing at the time of progression revealed a new SKAP2::BRAF fusion. She was then treated with a combination of selpercatinib and trametinib, which led to a likely partial response, despite the combination demonstrating side effects. This case report details the first known instance of NSCLC with a RET fusion developing resistance by means of a BRAF fusion, treated with combined RET and MEK inhibition.

Original language	English (US)
Article number	100724
Journal	JTO Clinical and Research Reports
Volume	5
Issue number	11
DOIs	https://doi.org/10.1016/j.jtocrr.2024.100724
State	Published - Nov 2024

Funding

Dr. Hines was supported by the National Institute for General Medical Sciences (T32 GM07019). The authors thank the patient's family for providing informed consent for this case report.

Keywords

Antineoplastic drug resistance
BRAF fusion
Case report
Molecular targeted therapy
Non–small cell lung cancer
RET fusion

ASJC Scopus subject areas

Oncology
Pulmonary and Respiratory Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jtocrr.2024.100724

Cite this

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title = "Combined RET and MEK Inhibition as a Treatment for RET Fusion-Positive NSCLC With Acquired BRAF Fusion: A Case Report",

abstract = "RET fusions are present in 1% to 2% of NSCLCs. Although RET inhibitors like selpercatinib are effective, resistance inevitably develops. We present the case of a 28-year-old female with recurrent NSCLC and a CCDC6::RET fusion treated with selpercatinib. Testing at the time of progression revealed a new SKAP2::BRAF fusion. She was then treated with a combination of selpercatinib and trametinib, which led to a likely partial response, despite the combination demonstrating side effects. This case report details the first known instance of NSCLC with a RET fusion developing resistance by means of a BRAF fusion, treated with combined RET and MEK inhibition.",

keywords = "Antineoplastic drug resistance, BRAF fusion, Case report, Molecular targeted therapy, Non–small cell lung cancer, RET fusion",

author = "Hines, {Jacobi B.} and Bowar, {Benjamin C.} and Margaret Colleton and Lydia Chelala and Peng Wang and Chadha, {Angad A.} and Jeremy Segal and Bestvina, {Christine M.}",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors",

year = "2024",

month = nov,

doi = "10.1016/j.jtocrr.2024.100724",

language = "English (US)",

volume = "5",

journal = "JTO Clinical and Research Reports",

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T1 - Combined RET and MEK Inhibition as a Treatment for RET Fusion-Positive NSCLC With Acquired BRAF Fusion

T2 - A Case Report

AU - Hines, Jacobi B.

AU - Bowar, Benjamin C.

AU - Colleton, Margaret

AU - Chelala, Lydia

AU - Wang, Peng

AU - Chadha, Angad A.

AU - Segal, Jeremy

AU - Bestvina, Christine M.

PY - 2024/11

Y1 - 2024/11

N2 - RET fusions are present in 1% to 2% of NSCLCs. Although RET inhibitors like selpercatinib are effective, resistance inevitably develops. We present the case of a 28-year-old female with recurrent NSCLC and a CCDC6::RET fusion treated with selpercatinib. Testing at the time of progression revealed a new SKAP2::BRAF fusion. She was then treated with a combination of selpercatinib and trametinib, which led to a likely partial response, despite the combination demonstrating side effects. This case report details the first known instance of NSCLC with a RET fusion developing resistance by means of a BRAF fusion, treated with combined RET and MEK inhibition.

AB - RET fusions are present in 1% to 2% of NSCLCs. Although RET inhibitors like selpercatinib are effective, resistance inevitably develops. We present the case of a 28-year-old female with recurrent NSCLC and a CCDC6::RET fusion treated with selpercatinib. Testing at the time of progression revealed a new SKAP2::BRAF fusion. She was then treated with a combination of selpercatinib and trametinib, which led to a likely partial response, despite the combination demonstrating side effects. This case report details the first known instance of NSCLC with a RET fusion developing resistance by means of a BRAF fusion, treated with combined RET and MEK inhibition.

KW - Antineoplastic drug resistance

KW - BRAF fusion

KW - Case report

KW - Molecular targeted therapy

KW - Non–small cell lung cancer

KW - RET fusion

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Combined RET and MEK Inhibition as a Treatment for RET Fusion-Positive NSCLC With Acquired BRAF Fusion: A Case Report

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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