Abstract 424P
Background
TETs are rare malignancies originating in the anterior mediastinum, with type B3 thymoma (T) and thymic carcinoma (TC) being the most aggressive subtypes. Lenvatinib (L) is a multi-tyrosine kinase inhibitor targeting VEGFR, FGFR, RET, c-Kit, and other kinases. A phase II clinical trial has demonstrated a progression-free survival (PFS) of 9.3 months with L 24 mg in TC. Real-world data on L benefit are limited.
Methods
We retrospectively selected patients (pts) with refractory TETs who received L as ≥2nd line treatment from 7 centers in France (part of the nationwide RYTHMIC network), and 1 U.S. center. Clinical and pathological characteristics were collected. PFS and overall survival (OS) were calculated using the initiation date of L. Toxicity and efficacy were evaluated locally, with adverse events graded according to the Common Terminology Criteria for Adverse Events v5.
Results
From Mar 2020 to Dec 2024, 43 pts were analyzed. Median age at diagnosis was 49 years (range: 24 to 71); 22 (51.2%) were female, autoimmune diseases were reported in 11 (25.6%) pts, withmyasthenia gravis being the most prevalent (7, 63.6%). TC (squamous cell) was identified in 23 cases (53.5%), followed by B3 T in 9 cases (20.9%) and T B2 in 5 cases (11.6%). L was used as a second-line treatment in 20 (46.5%), with 29 (67.4%) starting at 14 mg/day. 15 pts achieved a partial response (objective response rate of 34.9%); 19 pts experienced stable disease (disease control rate of 79.1%). The median follow-up was 27.0 months (95% CI: 10.2–43.8). The median PFS was 7.2 months (95% CI: 6.0–8.3) and the median OS was 27.0 months (95% CI: 15.5–38.5). For pts with TC, the PFS and OS were 8.00 (95% CI: 4.13–11.86) and 20.0 months (95% CI: 7.93–32.06), respectively. For pts with T, the PFS and OS were 6.86 (95% CI: 3.67–10.06) and 39 months (95% CI: 27.74–50.25). The most common toxicities were hypertension, fatigue, and mucositis, occurring in 17 (39.5%), 9 (21%), and 8 pts (18.6%), respectively. Grade 3–4 treatment-related adverse events were observed in 7 pts (16.3%). Dose reduction was required in 12 pts (29.3%).
Conclusions
We report the activity of L in pts with advanced T and TC, even when administered at lower doses than those used in the phase II trial. The toxicity profile was consistent with previously reported data.
Legal entity responsible for the study
Institut Gustave Roussy.
Funding
Has not received any funding.
Disclosure
J. Remon Masip: Financial Interests, Personal, Other, Travel, accomodation: Ose Immunotherapeutics; Financial Interests, Institutional, Invited Speaker: Janssen, Merck, Takeda; Non-Financial Interests, Personal, Principal Investigator, PI of PECATI trial in Thymic malignancies endorsed by a grant by MSD: MSD; Non-Financial Interests, Personal, Other, Co-PI of APPLE trial (EORTC-1525): AstraZeneca; Non-Financial Interests, Personal, Member, Secretary of the Lung Cancer Group at the EORTC: EORTC. N. Girard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Regeneron, AbbVie, Amgen, Lilly, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen, Pierre Fabre, BeiGene; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Pfizer, Amgen, MSD, Sanofi, Gilead, Janssen; Financial Interests, Personal, Officer: Edimark; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Other, Personal, Other, Family member is an employee: AstraZeneca. B. Besse: Financial Interests, Institutional, Advisory Board: AbbVie, Biontech SE, Beijing Aviston Biotechnology, Bristol Myer Squibb, CureVac AG, PharmaMar, Sanofi aventis, Regeneron; Financial Interests, Institutional, Expert Testimony: AbbVie, Bristol Myer Squibb, Eli Lilly, Ellipse pharma Ltd, CureVac AG, F.Hoffmann-La Roche Ltd, Foghorn Therapeutics Inc., Genmab, Immunocore, Owkin, Sanofi; Financial Interests, Institutional, Invited Speaker: AbbVie, AstraZeneca, Bristol Myer Squibb, MSD, Daiichi Sankyo, Eli Lilly, Ose Immunotherapeutics, Sanofi, Servier, Ose Immunotherapeutics, Sanofi, Takeda, Genmab, Taiho, AstraZeneca, Amgen, BeiGene, CureVac, Janssen, MSD, Pharmamar, Eli Lilly, Daiichi Sankyo, Enliven, Nuvalent, Ellipsis, Prelude Therapeutics; Non-Financial Interests, Personal, Leadership Role, Chair of the Scientific Chairs Council: EORTC; Non-Financial Interests, Personal, Advisory Role, Member of the Scientific Board: IFCT. All other authors have declared no conflicts of interest.