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. The pancreas was the most common primary site (n = 16, 48.5%), followed by the small bowel (n = 12, 36.4%). The median number of prior lines of systemic therapy was 2 (range 1-5). The median initial, maximal and minimal doses (mg) were 12 (range 4-24), 12 (range 8-24) and 8 (range 4-24), respectively. The median PFS was 11.9 months (95% CI, 9.5-NA), and the 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% (95% CI, 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.