Lung adenocarcinoma with RET fusion: early experience with diagnosis and targeted therapy

Date 27 March 2014
Event ELCC 2014
Session Proffered Papers 1 - Advanced disease with tageted agents
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Oliver Gautschi
Citation Journal of Thoracic Oncology (2014) 9 (Supplement 9): S7-S52. 10.1097/JTO.0000000000000131
Authors O. Gautschi1, G. Pall2, A. Schultheis3, F. Aebersold Keller4, M. Gardizi3, J. Heuckmann5, S. Merkelbach-Bruse3, J. Diebold4, J. Wolf6, L. Heukamp3
  • 1Klinik Für Onkologie, Luzerner Kantonsspital, 6004 - Luzern/CH
  • 2Innere Medizin, Universitätskliniken Innsbruck, 6020 - Innsbruck/AT
  • 3Institut Für Pathologie, Universitätsklinikum Köln, 50924 - Köln/DE
  • 4Institut Für Pathologie, Luzerner Kantonsspital, 6000 - Luzern/CH
  • 5Backfield Ag, Blackfield AG, 51105 - Köln/DE
  • 6Innere Medizin, Universitätsklinikum Köln, 50937 - Köln/DE

 

Abstract

Aim

Lung adenocarcinoma with RET fusion is a new diagnostic entity with potential clinical implications. Experience with diagnosis and targeted therapy is limited.

Methods

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.

Results

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.

Conclusions

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.

Disclosure

J. Heuckmann: Co-founder, shareholder and full time employee of Blackfield AG, Cologne, Germany All other authors have declared no conflicts of interest.