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RET Fusion Lung Carcinoma: Response to Therapy and Clinical Features in a Case Series of 14 Patients
Michal Sarfaty1, Assaf Moore2, Victoria Neiman1
1Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
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.
Insights
Rearranged during transfection (RET) fusions in lung adenocarcinoma present unique patterns, often with early visceral spread. Cabozantinib and chemotherapy show promising responses in these rare cases.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Rearranged during transfection (RET) fusions are found in 1-2% of lung adenocarcinoma (LADC).
- KIF5B-RET and CCDC6-RET are the most common RET fusion variants.
- The clinical behavior and treatment of RET-rearranged LADC require further elucidation.
Purpose of the Study:
- To describe the clinical characteristics and treatment outcomes of patients with RET-rearranged LADC.
- To evaluate the efficacy of targeted therapy and chemotherapy in this patient cohort.
Main Methods:
- Retrospective analysis of 14 LADC patients with RET fusions.
- Assessment of treatment response through clinical evaluation and avatar models.
- Analysis of specific RET fusion variants (KIF5B-RET, CCDC6-RET) and their clinical implications.
Main Results:
- KIF5B-RET and CCDC6-RET fusions were identified in 10 and 4 patients, respectively.
- KIF5B-RET fusions were associated with early disseminated disease, including visceral involvement.
- Cabozantinib demonstrated efficacy, achieving complete and partial responses. Platinum-based chemotherapy also showed durable responses.
Conclusions:
- RET-rearranged LADC, particularly KIF5B-RET, can present with aggressive features like early visceral involvement.
- Targeted therapy (cabozantinib) and chemotherapy offer potential treatment options for RET-rearranged LADC.
- Further research is necessary to optimize management strategies for this rare LADC subtype.
