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Published on: June 26, 2019
Acquired CD74-ROS1 fusion-mediated osimertinib resistance successfully treated with osimertinib and crizotinib: a
Ali Kaan Güren1, Erkam Kocaaslan1, Yeşim Ağyol1
1Division of Medical Oncology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey.
Abstract:
In EGFR T790M-mutant lung adenocarcinoma, the strong and early clinical responses achieved with osimertinib may be limited by the emergence of diverse resistance mechanisms over time. In this case report, we describe an acquired CD74-ROS1 fusion that developed during osimertinib therapy in a patient who had an EGFR exon 20 T790M mutation detected in the treatment-naive setting. The fusion, identified through a tissue biopsy performed at the time of progression, suggests that the tumor had activated an alternative oncogenic driver under therapeutic pressure. The combination of osimertinib and crizotinib resulted in a marked clinical and metabolic response, was well tolerated, and the patient remained in remission. This rare case highlights that acquired CD74-ROS1 fusions may contribute to osimertinib resistance and suggests that combination targeted therapy may represent a potential therapeutic approach in selected patients.
Insights
A rare acquired CD74-ROS1 fusion can cause resistance to osimertinib in EGFR-mutant lung cancer. Combination therapy with osimertinib and crizotinib showed promising results in this case.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- EGFR T790M-mutant lung adenocarcinoma often responds well to osimertinib.
- Resistance to osimertinib can develop over time due to various mechanisms.
- Acquired resistance mechanisms can involve alternative oncogenic drivers.
Purpose of the Study:
- To report a rare case of acquired CD74-ROS1 fusion developing during osimertinib therapy.
- To investigate the role of this fusion in osimertinib resistance.
- To evaluate the efficacy of combination targeted therapy.
Main Methods:
- Case report of a patient with EGFR exon 20 T790M mutation.
- Tissue biopsy at progression to identify acquired genetic alterations.
- Treatment with osimertinib and crizotinib combination therapy.
Main Results:
- An acquired CD74-ROS1 fusion was identified as a resistance mechanism.
- The combination of osimertinib and crizotinib led to significant clinical and metabolic response.
- The patient remained in remission and tolerated the treatment well.
Conclusions:
- Acquired CD74-ROS1 fusions can mediate resistance to osimertinib in EGFR-mutant lung adenocarcinoma.
- Combination targeted therapy may be a viable strategy for patients with acquired fusions.
- This case highlights the importance of identifying alternative oncogenic drivers under therapeutic pressure.
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