التفاصيل البيبلوغرافية
| العنوان: |
Erlotinib and Trametinib in Patients With EGFR -Mutant Lung Adenocarcinoma and Acquired Resistance to a Prior Tyrosine Kinase Inhibitor. |
| المؤلفون: |
Luo, Jia, Makhnin, Alex, Tobi, Yosef, Ahn, Linda, Hayes, Sara A., Iqbal, Afsheen, Ng, Kenneth, Arcila, Maria E., Riely, Gregory J., Kris, Mark G., Yu, Helena A. |
| المصدر: |
JCO Precision Oncology; 5/10/2021, Vol. 5, p55-64, 10p |
| مصطلحات موضوعية: |
PROTEIN-tyrosine kinase inhibitors, EPIDERMAL growth factor receptors, OVERALL survival, SURVIVAL rate, ERLOTINIB, SPEECH apraxia |
| مستخلص: |
PURPOSE: Inhibition of the MEK/ERK pathway is critical for Bcl-2-like protein 11 (BIM)-mediated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-induced apoptosis, and dysregulation of this pathway may be a mechanism of acquired resistance. Therefore, MEK inhibition with trametinib and an EGFR TKI may resensitize tumors with acquired resistance. Limited targeted therapies are available after progression on EGFR TKIs, and it is in this setting that we completed a phase I/II study of erlotinib and trametinib. METHODS: Patients with metastatic EGFR -mutant lung adenocarcinoma and acquired resistance to an EGFR TKI received combination erlotinib 75 mg and trametinib 1.5 mg daily until progression or unacceptable side effects. The primary objective was objective response rate determined using RECIST version 1.1. RESULTS: Twenty-three patients were accrued; patients had received a median of two lines of prior TKI therapy (61% prior osimertinib), and 48% had acquired EGFR T790M. We confirmed one partial response (1/23, 4%, 95% CI, 0 to 22). The median progression-free survival was 1.8 months, and the median overall survival was 21 months. Diarrhea (87%), acneiform rash (87%), and fatigue (52%) were the most common treatment-related adverse events. Two patients who had tumor shrinkage both harbored a BRAF fusion. CONCLUSION: Addition of trametinib to erlotinib in the acquired resistance setting in an unselected population is not efficacious. Future studies should focus on targeted therapies in molecularly selected populations. Acquired BRAF fusions in patients with EGFR -sensitizing mutations may be a molecular subset where EGFR and MEK combination therapy could be studied further. [ABSTRACT FROM AUTHOR] |
|
Copyright of JCO Precision Oncology is the property of American Society of Clinical Oncology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
