Background: TETs are rare malignancies of the anterior mediastinum being thymoma (T) B3 and thymic carcinoma (TC) the most aggressive subtypes. There is no standard treatment after platinum-based chemotherapy in refractory or metastatic setting. A phase 2 trial has reported clinical benefit for lenvatinib 24mg (objective response rate [ORR] of 38%), a novel multi-targeted inhibitor of VEGFR, FGFR, RET, c-Kit, and other kinases; significant toxicity grade 3 hypertension was 64%. No real-life data exists. Methods: We selected patients (pts) under lenvatinib as a second-line or beyond for refractory TETs from 8 International centers from France (belonging to the nationwide network RYTHMIC) and United States. We analyzed epidemiologic, clinical and pathological characteristics of patients with TET’s. The toxicity was evaluated according to CTCAE v4, with a local evaluation of efficacy and we assessed toxicity profile and survival outcomes. Results: From March 2020 to December 2021, 29 pts were enrolled. Median age at diagnosis was 49 (24-71), 51.7% were women, 6/29 (20.7%) reported auto-immune disorders (AIDs). TC was the most frequent subtype (n=18, 62.1%), followed by B3 and B2. Lenvatinib was used as a second line for 52% of pts, mainly starting from 14 mg/daily (n=20, 69%) and one pts with concomitant pembrolizumab. The ORR was 17% (95%CI 3.0-32.0) with partial responses only seen in TC, and the disease control rate was 76% (95%CI 59.0-92.0). Response was observed with the dose of 24mg in 3 pts and 14mg in 2 pts, with a median follow-up period of 5 months (m) (95%CI 3.2-6.7), PFS at 6 and 12 m was 64% and 30%, respectively. Toxicity is summarized in table 1. Dose de-escalations were needed in 27.5% of pts. Conclusions: We confirm the activity of lenvatinib in pts with advanced or metastatic T and TC, despite the use of lower doses than the phase 2 study.