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Response to Cabozantinib in patients with RET fusion-positive lung adenocarcinomas
Alexander Drilon1, Lu Wang, Adnan Hasanovic
1Departments of Medicine Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Abstract:
The discovery of RET fusions in lung cancers has uncovered a new therapeutic target for patients whose tumors harbor these changes. In an unselected population of non-small cell lung carcinomas (NSCLCs), RET fusions are present in 1% to 2% of cases. This incidence increases substantially, however, in never-smokers with lung adenocarcinomas that lack other known driver oncogenes. Although preclinical data provide experimental support for the use of RET inhibitors in the treatment of RET fusion-positive tumors, clinical data on response are lacking. We report preliminary data for the first three patients treated with the RET inhibitor cabozantinib on a prospective phase II trial for patients with RET fusion-positive NSCLCs (NCT01639508). Confirmed partial responses were observed in 2 patients, including one harboring a novel TRIM33-RET fusion. A third patient with a KIF5B-RET fusion has had prolonged stable disease approaching 8 months (31 weeks). All three patients remain progression-free on treatment.
Insights
RET fusions are a new target in lung cancer, especially in never-smokers. Early results show the RET inhibitor cabozantinib is effective, with partial responses and prolonged stable disease in RET fusion-positive non-small cell lung cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- RET fusions represent a novel therapeutic target in lung cancer.
- These fusions occur in 1-2% of non-small cell lung carcinomas (NSCLCs), with higher prevalence in never-smokers with adenocarcinoma lacking other drivers.
- Preclinical data support RET inhibitors, but clinical response data are limited.
Purpose of the Study:
- To evaluate the preliminary clinical efficacy of the RET inhibitor cabozantinib.
- To assess response rates in patients with RET fusion-positive NSCLCs.
- To report outcomes from a prospective Phase II clinical trial (NCT01639508).
Main Methods:
- Prospective Phase II clinical trial enrollment.
- Treatment with the RET inhibitor cabozantinib.
- Monitoring of patient response and progression-free survival.
Main Results:
- Two of the first three patients achieved confirmed partial responses.
- One patient had a novel TRIM33-RET fusion and responded.
- The third patient with a KIF5B-RET fusion achieved prolonged stable disease (31 weeks).
- All three patients remained progression-free during the observation period.
Conclusions:
- Cabozantinib demonstrates preliminary efficacy in patients with RET fusion-positive NSCLC.
- This suggests cabozantinib is a promising therapeutic option for this patient subset.
- Further investigation in a larger cohort is warranted to confirm these findings.
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