Clinical Outcomes of Pembrolizumab Combination Therapy in Heavily Pretreated PDTC and Anaplastic Thyroid Cancer.

Authors

Tim Brandenburg, Yara Maria Machlah, Lynn Marlene Srasra, Philipp Muchalla, Sarah Theurer, David Kersting, Manuel Maria Weber, Frank Weber, Henning Dralle, Harald Lahner, Dagmar Führer

Published in

European thyroid journal. Sep 28, 2026. Epub Sep 28, 2026.

Abstract

Poorly differentiated (PDTC) and anaplastic thyroid carcinoma (ATC) are rare, aggressive malignancies with limited treatment options. Although targeted therapies for tumours harbouring BRAF V600E mutations or fusions involving NTRK1, NTRK2, NTRK3, or RET have expanded treatment options, most patients lack such actionable alterations and urgently require alternative therapeutic strategies. Immune checkpoint blockade (ICB) has emerged as a promising approach, but its real-world application is limited by restricted trial access, reimbursement challenges, and the aggressive course of these diseases.
We retrospectively analysed the Essen ATC/PDTC cohort (June 2018 - February 2024) to evaluate the real-world efficacy of lenvatinib plus pembrolizumab (LEN-PEM) in heavily pretreated patients, including PDTC cases progressing after ≥2 prior tyrosine kinase inhibitors and ATC cases treated with upfront (radio-)chemotherapy.
Among the five patients with PDTC, four achieved a partial response, and one achieved durable stable disease (>50 months), corresponding to an objective response rate (ORR) of 4/5 and a clinical benefit rate (CBR) of 5/5. Median progression-free survival (PFS) and overall survival (OS) from LEN-PEM initiation were 29.1 and 34.9 months, respectively; median OS from diagnosis was not reached. Among the ten patients with ATC, four achieved a partial response, and three achieved stable disease, corresponding to an ORR of 4/10 and a CBR of 7/10. Median PFS and OS from LEN-PEM initiation were 7.6 and 9.9 months, respectively, and median OS from diagnosis was 24.3 months.
LEN-PEM demonstrates meaningful clinical activity in pretreated PDTC and ATC patients, supporting its use as a later-line therapeutic option.

PMID:
42804425
Bibliographic data and abstract were imported from PubMed on 29 Sep 2026.

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