@article{36815159dae44dd2a17efcf79178c07a,
title = "Phase II trial of cabozantinib plus erlotinib in patients with advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer with progressive disease on epidermal growth factor receptor tyrosine kinase inhibitor therapy: A California cancer consortium phase II trial (NCI 9303)",
abstract = "Introduction: Mesenchymal epidermal transition and vascular endothelial growth factor pathways are important in mediating non-small cell lung cancer (NSCLC) tumorigenesis and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance. We hypothesized that treatment with cabozantinib plus erlotinib in EGFR mutation-positive NSCLC following progression on EGFR TKI therapy may allow tumors to overcome this resistance or restore sensitivity to therapy regardless of T790M status. Methods: Patients with advanced NSCLC, known EGFR mutation and progressive disease on an EGFR TKI immediately prior to enrollment without intervening therapy were enrolled. Patients received erlotinib 150 mg and cabozantinib 40 mg daily. The primary endpoint was evaluation of efficacy by objective response rate. Secondary endpoints included assessment of progression free survival (PFS), overall survival, change in tumor growth rate, safety and toxicity, and the evaluation of specific EGFR mutations and MET amplification in pre-treatment tissue and plasma. Results: Thirty-seven patients were enrolled at 4 centers. Four patients had partial response (10.8%) and 21 had stable disease (59.5%). A greater than 30% increase in tumor doubling time was observed in 79% of assessable patients (27/34). Median PFS was 3.6 months for all patients. Diarrhea (32%) was the most common grade 3 adverse event; 3 patients had asymptomatic grade 4 elevation of amylase and lipase. Conclusions: Combination erlotinib and cabozantinib demonstrates activity in a highly pretreated population of patients with EGFR mutation and progression on EGFR TKI. Further elucidation of beneficial patient subsets is warranted.",
author = "Reckamp, {Karen L.} and Frankel, {Paul H.} and Nora Ruel and Mack, {Philip C.} and Gitlitz, {Barbara J.} and Tianhong Li and Marianna Koczywas and Gadgeel, {Shirish M.} and Cristea, {Mihaela C.} and Belani, {Chandra P.} and Newman, {Edward M.} and Gandara, {David R.} and Lara, {Primo N.}",
note = "Funding Information: Supported by NCI-CTEP N01 CM-00038 awarded to the University of California Davis (Phase II headquarters of the California Cancer Consortium; Principal Investigator: PL). Research reported in this publication included work performed in the City of Hope Comprehensive Cancer Center Pathology Core supported by the National Cancer Institute of the National Institutes of Health under award number P30CA033572. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: This work was kindly supported by academic grants from the National Institute of Health Research{\textquoteright}s Health Technology Assessment Unit and from Cancer Research UK. Publisher Copyright: Copyright {\textcopyright} 2019 Reckamp, Frankel, Ruel, Mack, Gitlitz, Li, Koczywas, Gadgeel, Cristea, Belani, Newman, Gandara and Lara. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.",
year = "2019",
doi = "10.3389/fonc.2019.00132",
language = "English (US)",
volume = "9",
journal = "Frontiers in Oncology",
issn = "2234-943X",
publisher = "Frontiers Media S. A.",
number = "MAR",
}