Abstract 1915P
Background
Anaplastic thyroid carcinoma (ATC) and poorly differentiated thyroid carcinoma (PDTC) have a dismal prognosis despite multimodal therapy. Tumors are high proliferative, with increased mutational burden (TMB) and enhanced PD-L1 levels, implicating effectiveness of antiproliferative agents (lenvatinib) and immune checkpoint inhibitors (pembrolizumab).
Methods
The lenvatinib/pembrolizumab combination was examined within a prospective phase II trial (ATLEP, Anaplastic Thyroid Carcinoma Lenvatinib Pembrolizumab, EudraCT No. 2017-004570-3) in 20 ATC/PDTC pts (16 ATC/4 PDTC), and in a retrospective study including 8 pts (6 ATC/2 PDTC) and follow up over 3 years. Lenvatinib was started with 20/24 mg daily; pembrolizumab (200 mg) was given i.v. every 3 weeks for up to 36 months. Patient tumors were characterized by WES and PD-L1 expression (TPS 1-90%).
Results
a) Retrospective analysis: BOR in ATCs was 66% CR (4/6), 16% SD and 16% PD. BOR in PDTCs was PR (2/2). Median PFS was 17.75 mo for all pts, and 16.5 mo for ATCs, with treatment durations ranging from 1 to 40 mo. Grade III/IV toxicities evolved in 4/8 pts, requiring dose reduction/discontinuation of lenvatinib. Median OS was 18.5 mo for all pts, and 17.5 mo for ATCs, with 3 ATC being alive without relapse (40, 27 and 19 mo) despite metastasized disease at treatment start. All pts with long-term (> 2 years) or CR had either increased TMB or PD-L1 TPS > 50%. b) ATLEP trial: The primary endpoint ORR at 3 months was reached for all 20 pts and is 30% (6/20 PR). Current BOR is 40% PR for all pts (8/20) and 37.5% PR for ATCs only (6/16). All other pts have reached a SD: 60% SD (12/20) for all, 62.5% SD for ATCs only (10/16). PFS and OS are not reached. CTCAE grade III/IV toxicities included aspergillus pneumonia (3/20 pts), hemorrhage (2/20) and fistulas (3/20).
Conclusions
Our results implicate that a combination of lenvatinib and pembrolizumab is safe and effective in patients with ATC or PDTC, including complete and long-term remissions. As the primary endpoint was reached, the phase II ATLEP trial will be extended to 20 more patients (20 ATCs/20 PDTCs total).
Clinical trial identification
2017-004570-3.
Editorial acknowledgement
Legal entity responsible for the study
University of Freiburg.
Funding
University of Freiburg.
Disclosure
All authors have declared no conflicts of interest.