115P - KIF5B & CCDC6 RET in lung cancer: Clinical insights and response to personalized based therapy

Date 17 April 2015
Event ELCC 2015
Session Poster lunch
Topics Non-Small-Cell Lung Cancer, Metastatic
Personalised Medicine
Presenter Michal Sarfaty
Citation Annals of Oncology (2015) 26 (suppl_1): 29-44. 10.1093/annonc/mdv050
Authors M. Sarfaty1, A. Moore1, M. Gottfried2, R. Katznelson3, H. Nechushtan4, M. Wolner5, V. Neiman1, L. Soussan-Gutman6, A. Dvir7, N. Peled1
  • 1Oncology, Rabin Medical Center Davidoff Cancer Centre, Beilinson Campus, 4941492 - Petach Tikva/IL
  • 2Institute Of Oncology, Meir Medical Center, Kfar Saba/IL
  • 3Institute Of Oncology, Kaplan Medical Center Oncology Institute, Rehovot/IL
  • 4Sharett Institute Of Oncology, Hadassah Ein Kerem, Jerusalem/IL
  • 5Institute Of Oncology, Rambam Health Care Center, Haifa/IL
  • 6Teva Pharmaceutical Industries Ltd., Petach Tikva/IL
  • 7Teva Pharmaceutical Industries Ltd., Teva Pharmaceutical Industries Ltd., Petach Tikva/IL

Abstract

Aim/Background

Gene analysis became a key factor in managing lung adenocarcinomas (LADC). Rearrangements during transfection (RET) mutations have been reported in 1-2% of LADC, where KIF5B-RET fusion is more common (70-90%) than CCDC6-RET (10-25%). The natural history and the management of RET mutated lung cancer are still unclear. We hereby present a series of eight RET-mutated lung cancer patients, as the first series of lung cancer patients harboring RET fusions out of a clinical study.

Methods

This is a multicenter, retrospective report of eight lung cancer patients who harbored RET fusion between May 2009 and July 2014.

Results

Four males and four women, mean age of 51 years (range 28-72), four were never and four light smokers. Five harbored the KIF5B-RET variant and three the CCDC6-RET. Five cases had hyper-acute presentation and/or recurrence. Four of them harbored the KIF5B variant. Among them, one patient (KIF5B-RET) treated with cabozantinib and showed a rapid and durable complete response by Response Evaluation Criteria in Solid Tumors for 8 months. Interestingly enough, unique characteristic included bilateral miliary lung metastasis on presentation and early abdominal (liver, ovaries, intestinal) and bone involvement. To our knowledge, this is the first study to report a complete response to cabozantinib for this indication. One patient (with CCDC6-RET mutation) displayed a profound and durable response to cisplatin/pemetrexed/bevacizumab therapy of 8 months.

Conclusions

RET-fusion LADC may have an abrupt and acute presentation; in our series, tend to be associated with KIF5B subtype. While some RET-fusion positive LADC patients might benefit from combination chemotherapy, it may also be that the most effective targeted therapy is cabozantinib with a potential long standing complete response. The dose, rate and duration of response need to be further assessed in large randomized control trials.

Disclosure

L. Soussan-Gutman and A. Dvir: Work at Teva Pharmaceutical Industries Ltd.

All other authors have declared no conflicts of interest.