Lung adenocarcinoma with RET fusion: early experience with diagnosis and targeted therapy
|Date||27 March 2014|
|Session||Proffered Papers 1 - Advanced disease with tageted agents|
|Topics|| Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
|Citation||Journal of Thoracic Oncology (2014) 9 (Supplement 9): S7-S52. 10.1097/JTO.0000000000000131|
O. Gautschi1, G. Pall2, A. Schultheis3, F. Aebersold Keller4, M. Gardizi3, J. Heuckmann5, S. Merkelbach-Bruse3, J. Diebold4, J. Wolf6, L. Heukamp3
Lung adenocarcinoma with RET fusion is a new diagnostic entity with potential clinical implications. Experience with diagnosis and targeted therapy is limited.
In November 2012, we integrated RET break-apart fluorescence in-situ hybridization (FISH) into our diagnostic test algorithms for primary lung adenocarcinoma. Positive cases were recorded in our databases, and clinical outcomes were collected from patients who received RET inhibitors on an individual compassionate use or off-label use basis. Next generation sequencing and PCR were performed on selected diagnostic and repeat biopsy samples, to identify RET kinase mutations and fusion partners. All patients with targeted therapy consented to treatment, translational research and publication.
By November 2013, 529 consecutive tumor samples were analysed by RET-FISH in our diagnostic laboratories. Twelve (2.3%) samples were positive, and none carried a secondary mutation in EGFR, HER2, KRAS, BRAF, ALK, or ROS1. So far, 4 pts with RET fusion and previous chemotherapy received one or more lines of targeted therapy. One pt received sunitinib and had prolonged disease stabilization. Three pts received vandetanib as first targeted therapy and 2 had a response. The same 3 pts received cabozantinib as second targeted therapy after progression on vandetanib. Two pts had a response to cabozantinib and one pt started with ponatinib recently. Three pts had tumor rebiopsy after targeted therapy. Molecular analyses are ongoing and updated results will be presented at the meeting.
The incidence of RET fusion was higher than expected, and preliminary activity of targeted therapy was confirmed. Of note, we observed preliminary activity of cabozantinib in pretreated tumors with primary and secondary resistance to vandetanib. Activation of a global phase II trial with cabozantinib in RET fusion positive lung cancer is planned. Clinicians should be aware of it, and refer eligible patients to participating centers.
J. Heuckmann: Co-founder, shareholder and full time employee of Blackfield AG, Cologne, Germany All other authors have declared no conflicts of interest.