1646MO - Phase II ATLEP trial: Final results for lenvatinib/pembrolizumab in metastasized anaplastic and poorly differentiated thyroid carcinoma

Background

Anaplastic thyroid carcinoma (ATC) patients without a BRAF mutation have a dismal prognosis despite extensive multimodal therapy. In a retrospective analysis we have previously shown the combination of lenvatinib/pembrolizumab to be effective for ATC/PDTC patients with elevated PD-L1 expression or high mutation frequency. Within the ATLEP trial, we therefore prospectively investigated the effect of the lenvatinib/pembrolizumab combination in ATC and PDTC patients.

Methods

The combination of lenvatinib/pembrolizumab was examined within a prospective phase II trial (ATLEP, Anaplastic Thyroid Carcinoma Lenvatinib Pembrolizumab, EudraCT No. 2017-004570-3) involving 27 ATC pts and 8 PDTC pts. ATCs and PDTCs were all metastasized (Stage IV), mainly pretreated with chemotherapy/radiotherapy and surgery (>90%), and lacked a B-RAF V617F mutation. Lenvatinib was started with 20 mg per day, and pembrolizumab (200 mg) was given i.v. every 3 weeks for up to two years. The primary endpoint was defined as ORR of > 10% after 3 months of treatment. Tumors were genotyped by whole exome sequencing (WES) and analyzed for PD-L1 expression.

Results

Of 39 screened pts, 35 could be evaluated for treatment response at 3 mo of treatment. The primary endpoint ORR at 3 mo was achieved, and was 34.3% (12/35 PR) for all patients. For ATCs the BOR (best overall response) within two treatment years was 51.9% PR (14/27) and 44.4% SD (12/27). For PDTCs, BOR was 75% PR (6/8) and 25% SD (2/8). The Clinical Benefit Rate (CBR) was 96.3% for ATC (26/27) and 100% for PDTC (8/8). For ATCs, the median PFS was 9.5 mo and the OS 10.25 mo. 25.9% of the ATC patients survived more than 2 years (7/27). For PDTCs, the median PFS was 20 months, while median OS has not been reached. CTCAE grade III/IV toxicities included hemorrhage after fistula development, autoimmune hepatitis, pulmonary embolism and infectious complications including aspergillus pneumonias. Biomarker assessment (PD-L1 status, WES) will be available at presentation.

Conclusions

Our results implicate that a combination of lenvatinib and pembrolizumab is safe and effective in patients with ATC and PDTC, and induces high response rates including long-lasting remissions.

Clinical trial identification

EudraCT 2017-004570-3.

Editorial acknowledgement

Legal entity responsible for the study

C. Dierks.

Funding

Eisai funded the drug Lenvatinib.

Disclosure

All authors have declared no conflicts of interest.