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A phase 2 study of lenvatinib in patients with RET fusion-positive lung adenocarcinoma
Toyoaki Hida1, Vamsidhar Velcheti2, Karen L Reckamp3
1Department of Thoracic Oncology, Aichi Cancer Center Hospital, 1-1, Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan.
Objectives:
Despite improved outcomes associated with immunotherapies for non-small cell lung cancer (NSCLC), many patients do not respond to treatment. Therefore, there is still an unmet need for molecularly targeted therapies in this patient population. Fusions of the RET oncogene have been identified as driver alterations in patients with NSCLC. Lenvatinib is a multityrosine kinase inhibitor of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, RET, and other targets. This study evaluated the safety and efficacy of lenvatinib in patients with RET fusion-positive lung adenocarcinoma.
Materials And Methods:
In this phase 2, multicenter, open-label study (NCT01877083), patients with RET-positive lung adenocarcinoma received oral lenvatinib 24 mg/day. The primary end point was objective response rate (ORR) by investigator review per Response Evaluation Criteria In Solid Tumors v1.1 criteria. The secondary end points included safety and tolerability, progression-free survival (PFS), and overall survival (OS).
Results:
Of 536 patients who screened for study inclusion and exclusion, 25 patients with RET translocations (KIF5B-RET [n = 13] and CCDC6-RET [n = 12]) were identified and received lenvatinib. The overall ORR was 16% (95% CI: 4.5%-36.1%). At data cutoff (February 3, 2016), the median PFS was 7.3 months (95% CI: 3.6-10.2) and the median OS was not reached. Duration of response was not estimable at the time of data cutoff. All patients experienced a treatment-emergent adverse event (TEAE); 23 (92%) patients experienced a TEAE of ≥ grade 3, and 6 (24%) patients discontinued lenvatinib due to a TEAE. The most common TEAEs were hypertension (68%), nausea (60%), decreased appetite (52%), diarrhea (52%), and proteinuria (48%).
Conclusions:
Lenvatinib demonstrated activity in patients with RET fusion-positive lung adenocarcinomas; although the response rate was relatively low, the median PFS supports the activity of lenvatinib in these patients.
Insights
Lenvatinib showed activity in non-small cell lung cancer patients with RET fusions. Despite a low response rate, median progression-free survival suggests lenvatinib
Area of Science:
- Oncology
- Molecular targeted therapy
- Lung cancer research
Background:
- Immunotherapies improve non-small cell lung cancer (NSCLC) outcomes, but many patients lack response.
- RET oncogene fusions are key driver alterations in a subset of NSCLC patients.
- Targeted therapies are needed for NSCLC patients unresponsive to current treatments.
Purpose of the Study:
- To evaluate the safety and efficacy of lenvatinib in patients with RET fusion-positive lung adenocarcinoma.
- To determine the objective response rate (ORR) of lenvatinib in this patient population.
- To assess progression-free survival (PFS) and overall survival (OS) as secondary endpoints.
Main Methods:
- Phase 2, multicenter, open-label study (NCT01877083).
- 25 patients with RET translocations (KIF5B-RET or CCDC6-RET) received oral lenvatinib 24 mg/day.
- Primary endpoint: ORR by investigator review; Secondary endpoints: safety, tolerability, PFS, OS.
Main Results:
- Overall ORR was 16% (95% CI: 4.5%-36.1%).
- Median PFS was 7.3 months (95% CI: 3.6-10.2); median OS was not reached.
- Most common treatment-emergent adverse events (TEAEs) included hypertension, nausea, decreased appetite, diarrhea, and proteinuria. 92% of patients experienced grade ≥3 TEAEs.
Conclusions:
- Lenvatinib demonstrated clinical activity in patients with RET fusion-positive lung adenocarcinomas.
- While the ORR was modest, the median PFS supports lenvatinib's efficacy in this specific NSCLC subgroup.
- Further investigation may be warranted for lenvatinib in RET-altered lung cancer.
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