Real-world outcomes of lenvatinib therapy for advanced neuroendocrine neoplasms

Advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) constitute a heterogeneous group of incurable cancers. Lenvatinib is an oral multiple kinase inhibitor that showed activity in grade 1/2 GEP-NENs in the phase II TALENT trial, but a confirmatory phase III study has yet to be conducted. To investigate the real-world use of lenvatinib in treating patients with advanced GEP-NENs, we retrospectively analyzed a cohort of adults with unresectable neuroendocrine neoplasms (NENs) from two academic centers in Canada who received palliative treatment with lenvatinib. Progression-free survival (PFS), overall survival (OS), and the treating clinician assessment of best therapeutic response were analyzed in the entire cohort and in the subgroup of patients with GEP-NENs that would have been eligible for the TALENT trial. Overall, 33 patients with mostly G1/G2 (78.8%) metastatic NENs received lenvatinib. Pancreas was the most common primary site (n=16, 48.5%), followed by small bowel (n=12, 36.4%). Median prior lines of systemic therapy were 2 (range 1-5). Median initial, maximal, and minimal doses (mg) were 12 (range 4-24), 12 (range 8-24), and 8 (range 4-24). Median PFS was 11.9 months (95%CI, 9.5-NA), and median OS was 17.5 months (95%CI 12.7-NA), with disease burden reduction seen in 21.9% (95% CI, 11.0-38.7) and 87.5% (71.9-95.3) of patients achieving disease control. The most frequent side effects reported were hypertension (60.6%), fatigue (39.4%), hypothyroidism (21.2%), and diarrhea (18.2%). This real-world cohort demonstrates encouraging evidence of lenvatinib activity in metastatic NENs, even when used at lower doses than previously studied in NENs.