In a phase II trial (TALENT; GETNE1509) reported in the Journal of Clinical Oncology, Jaume Capdevila, MD, and colleagues found that lenvatinib produced durable responses in patients with previously treated advanced grade 1 or 2 gastroenteropancreatic neuroendocrine tumors.

Jaume Capdevila, MD

Study Details

In the trial, 111 patients were enrolled from sites in four European countries between September 2015 and March 2017, including 55 with pancreatic neuroendocrine tumors (panNET cohort) and 56 with gastrointestinal neuroendocrine tumors (GI-NET cohort). Documented disease progression after treatment with a targeted agent was required for panNET patients or with somatostatin analogs for GI-NET patients.

Patients received lenvatinib at 24 mg once daily until disease progression or treatment intolerance. The primary endpoint was overall response rate on central radiology review.

Responses

Median follow-up was 23 months. Responses (all partial) were observed in 32 patients (29.9%, 95% confidence interval [CI] = 21.6%–39.6%) in the total population, 23 (44.2%, 95% CI = 30.7%–58.6%) in the panNET cohort, and 9 (16.4%, 95% CI = 8.2%–29.3%) in the GI-NET cohort. An additional 69 (64.5%), 27 (51.9%), and 42 patients (76.4%) had stable disease, yielding disease control rates of 94.4%, 96.2%, and 92.7%. Median response durations were 21.5 months (range = 8.4–38.3 months), 19.9 months (range = 8.4–30.8 months), and 33.9 months (range = 10.6–38.3 months).

Median progression-free survival was 15.7 months (95% CI = 14.1–19.5 months) in the total population, 15.6 months (95% CI = 11.4 months–not reached) in the panNET cohort, and 15.7 months (95% CI = 12.1–19.5 months) in the GI-NET cohort. Median overall survival was 32 months (95% CI = 26.47 months–not reached) in the panNET cohort and not reached in the GI-NET cohort.

Adverse Events

Among grade 3 or 4 adverse events, the most common were hypertension (21.8%), vomiting (9.1%), and diarrhea and abdominal pain (7.3% each) in the panNET cohort and hypertension (23.2%), asthenia (16.1%), and diarrhea (14.3%) in the GI-NET cohort. Dose reduction and treatment interruption occurred in 81.1% and 92.8% of patients. Adverse events led to discontinuation of treatment in 16 patients (14.4%) in the total population, including 6 (10.9%) in the panNET cohort and 10 (17.8%) of the GI-NET cohort.

The investigators concluded, “We report the highest centrally confirmed response reported to date with a multikinase inhibitor in advanced gastroenteropancreatic neuroendocrine tumors, with a particularly strong response in the panNET cohort. This study provides novel evidence for the efficacy of lenvatinib in patients with disease progression following treatment with other targeted agents, suggesting the potential value of lenvatinib in the treatment of advanced gastroenteropancreatic neuroendocrine tumors.”

Jaume Capdevila, MD, PhD, of Vall d’Hebron Institute of Oncology, Barcelona, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The investigator-initiated trial is sponsored by the Spanish Task Force for Neuroendocrine and Endocrine Tumors (GETNE) with financial support from Eisai. For full disclosures of the study authors, visit ascopubs.org.