RET Fusion Lung Carcinoma: Response to Therapy and Clinical Features in a Case Series of 14 Patients

Michal Sarfaty, Assaf Moore, Victoria Neiman, Elizabeth Dudnik, Maya Ilouze, Maya Gottfried, Rivka Katznelson, Hovav Nechushtan, Hadas Gantz Sorotsky, Keren Paz, Amanda Katz, Milton Saute, Mira Wolner, Mor Moskovitz, Vincent Miller, Julia Elvin, Doron Lipson, Siraj Ali, Lior Soussan Gutman, Addie DvirNoa Gordon, Nir Peled

Research output: Contribution to journalArticlepeer-review

Abstract

Data are increasing regarding RET (rearranged during transfection) fusions in lung cancer. We present our experience with the natural history of this disease and its response to targeted therapy and standard chemotherapy in 14 patients. In our series, RET-rearranged lung adenocarcinoma had an early disseminated presentation, especially with KIF5B fusion. Treatment with cabozantinib achieved responses, including 1 complete response. Background RET (rearranged during transfection) fusions have been reported in 1% to 2% of lung adenocarcinoma (LADC) cases. In contrast, KIF5B-RET and CCDC6-RET fusion genes have been identified in 70% to 90% and 10% to 25% of tumors, respectively. The natural history and management of RET-rearranged LADC are still being delineated. Materials and Methods We present a series of 14 patients with RET-rearranged LADC. The response to therapy was assessed by the clinical response and an avatar model in 2 cases. Patients underwent chemotherapy, targeted therapy, and immunotherapy. Results A total of 14 patients (8 women; 10 never smokers; 4 light smokers; mean age, 57 years) were included. KIF5B-RET and CCDC6-RET variants were diagnosed in 10 and 4 cases, respectively. Eight patients had an early disseminated manifestation, seven with KIF5B-RET rearranged tumor. The features of this subset included bilateral miliary lung metastases, bone metastases, and unusual early visceral abdominal involvement. One such patient demonstrated an early and durable complete response to cabozantinib for 7 months. Another 2 patients treated with cabozantinib experienced a partial response, with rapid significant clinical improvement. Four patients with tumors harboring CCDC6-RET and KIF5B-RET fusions showed pronounced and durable responses to platinum-based chemotherapy that lasted for 8 to 15 months. Two patients' tumors showed programmed cell death ligand 1-positive staining but did not respond to pembrolizumab. The median overall survival was 22.8 months. Conclusion RET-rearranged LADC in our series tended to occur as bilateral disease with early visceral involvement, especially with KIF5B fusion. Treatment with cabozantinib achieved responses, including 1 complete response. However, further studies are required in this group of patients.

Original languageEnglish
Pages (from-to)e223-e232
JournalClinical Lung Cancer
Volume18
Issue number4
DOIs
StatePublished - Jul 2017

Keywords

  • Cabozantinib
  • Lung cance
  • PDL-1
  • Personalized medicine
  • RET

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