PSAT385 Single Center Experience with the Combination of Lenvatinib and Pembrolizumab for the Treatment of Anaplastic Thyroid Cancer

INTRODUCTION: Anaplastic thyroid cancer (ATC) is rare with a poor prognosis. There are no approved treatments for non-BRAF-mutated ATCs, leading to an unmet need. Phase II studies of single-agent lenvatinib or immunotherapy showed minimal benefit (lenvatinib: overall response rate (ORR) 2.9%, progression free survival (PFS) 2.6 months, overall survival (OS) 3.2 months; spartalizumab: ORR 19%, PFS 1.7 months, OS 5.9 months). Synergism between lenvatinib and pembrolizumab (L/P) has been reported. We sought to assess the efficacy and safety of L/P in ATC. METHODS: Thisis a retrospective, single-center study of ATC patients treated with L/P, between 1/2015-10/2021. L/P had to be started before first restaging. Those with pembrolizumab added at the time of progression on lenvatinib alone were excluded. The endpoints were ORR and PFS (primary) and OS and safety (secondary). Response evaluation was assessed by a single radiologist using RECIST v1.1. Treatment start date was the date of either lenvatinib or pembrolizumab initiation. RESULTS: 18 patients were included: 61% men; median age 64; initial stage: IVA (17%), IVB (11%), IVC (72%); common distant metastases: lung (83%), mediastinum (39%), bone (22%). Previous therapies: surgery (78%), chemoradiation (39%), cytotoxic chemotherapy (11%), palliative neck radiation (17%), BRAF-targeted therapy (6%), and immunotherapy (6%). All patients had mutation testing, and the common included TP53 (67%), PTEN (50%), TERTp (39%), NF1 (28%), RAS (22%), PIK3CA (17%), BRAF-V600E (6%). 11/12 tested tumors had a PDL-1 score >1%. Lenvatinib was started at 14-24 mg daily. With respect to lenvatinib, pembrolizumab was started from -14 to +49 days (median +6 days) at a fixed dose of 200 mg every 3 weeks. ORR was evaluable in 12 patients (outside hospital restaging scans unavailable in 6 patients): 1/12 (8%) confirmed complete response, 7/12 (58%) partial response (3 confirmed), 2/12 (17%) stable disease, and 2/12 (17%) progressive disease. The median PFS was 4.1 months (95% CI, 2.2 to NA), with treatment durations ranging from 0.5-33.5 months. The median OS of the 18 patients was 6.2 months (95% CI, 4.6 to NA). Respective 12-month PFS and OS rates were 25% and 22%. Grade III/IV toxicities were fatigue (22%); anorexia, weakness, arthralgia, dry mouth, pneumonitis (6%, each). AEs leading to death were pulmonary hemorrhage (17%), gastrointestinal bleed, pulmonary embolism (6%, each). Lenvatinib dose reduction, interruption, and discontinuation rates were 28%, 6%, and 28%, respectively. Pembrolizumab dose interruption and discontinuation rates were 6% and 11%, respectively. CONCLUSIONS: The combination L/P had an ORR of 66%. Although most responses were short-lived, a quarter of patients benefited for more than 1 year. The ORR, PFS, and OS were better than lenvatinib alone. The toxicity profile was as expected. Our results represent the largest single-institution experience thus far with L/P in ATC and warrant further investigation (NCT04171622). Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.