| General information |
| Database: | DB00093 |
| Objective: | The discovery of RET fusions in lung cancers has uncovered a new therapeutic target for patients whose tumors harbor these changes.Here reported preliminary data for the first three patients treated with the RET inhibitor cabozantinib on for patients with RET fusionpositive non small cell lung cancers |
| Authors: | Drilon A, et al |
| Title: | Response to Cabozantinib in patients with RET fusionpositive lung adenocarcinomas. |
| Journal: | Cancer Discov. |
| Year: | 2013 |
| PMID: | 23533264 |
| Trial Design |
| Clinical Trial Id: | NCT01639508 |
| Agent: | cabozantinib
|
| Target: | Hepatocyte growth factor receptor, Vascular endothelial growth factor receptor 2
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced ¡°pannegative¡± nonsquamous non small cell lung cancers (Pannegative status was defined as the absence of mutations in EGFR, KRAS, NRAS, BRAF, human epidermal growth factor receptor 2, PIK3CA, MAP2K1, and AKT and fusions of ALK and ROS1) |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a prospectivephase II trial |
| Key Patients Feature: | patients with pathologic or cytologic evidence of non small cell lung cancer, clinical stage IV or recurrent/medically inoperable disease, a Karnofsky performance status of more than 70%, a life expectancy of more than 12 weeks, adequate hematologic, renal, and hepatic function, measurable disease, and positive testing for a RET fusion via RTPCR or FISH. |
| Biomarker: | RET gene rearrangements |
| Biomark Analysis: | A third patient with a KIF5BRET fusion has had prolonged stable disease approaching 8 months (31 weeks). |
| Control Group Info: | single arm |
| Treatment Info: | Patients receive cabozantinib at 60 mg orally daily in 28day cycles until disease progression or unacceptable toxicity. |
| Primary End Point: | objective response at 12 weeks via RECIST v1.1. |
| Secondary End Point: | progression free survival, overall survival, and grade 3 or 4 treatmentrelated adverse events |
| Patients Number: | 3 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | Confirmed partial responses were observed in 2 patients, including one harboring a novel TRIM33RET fusion. A third patient with a KIF5BRET fusion has had prolonged stable disease approaching 8 months (31 weeks). |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | All three patients remain progression free on treatment. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | toxicities were manageable |
| Conclusions: | their series of treatment responses to cabozantinib in patients with RET fusionpositive tumors provides the first clinical data for a new target and drug treatment paradigm in lung cancers. Cabozantinib administration was feasible and toxicities were manageable. RET fusions represent a new addition to the growing list of actionable drivers in lung cancers and merit continued investigation. |