Dataset Information

Pembrolizumab in a Patient with Treatment-Naive Unresectable BRAF-Mutation Negative Anaplastic Thyroid Cancer.

ABSTRACT: Immune check point inhibitor (ICI) therapy can be a potentially effective salvage treatment for anaplastic thyroid cancer (ATC) with progression despite standard of care therapies. We report a case of unresectable treatment-naïve ATC showing a dramatic and durable response to first-line pembrolizumab therapy. A 69-year-old male presented with a large, right-sided neck mass associated with compressive symptoms. A neck ultrasound showed a large, right-sided, and highly suspicious thyroid nodule. A fine needle aspiration (FNA) biopsy revealed tumor cells consistent with ATC that were positive for PD-L1, with an expression score of >95% and negative for the BRAF V600E mutation. Imaging studies were negative for distant metastases. The disease was declared surgically inoperable, and the patient declined chemotherapy/radiation therapy (XRT), but agreed to ICI therapy with intravenous pembrolizumab 200 mg every three weeks. The patient has received 25 doses of pembrolizumab to date, with rapid resolution of symptoms and a significant reduction in tumor size. He remains alive without disease progression 18 months since initial diagnosis.

SUBMITTER: Nabhan F

PROVIDER: S-EPMC8166484 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Pembrolizumab in a Patient with Treatment-Naïve Unresectable BRAF-Mutation Negative Anaplastic Thyroid Cancer.

Nabhan Fadi F Kander Elizabeth E Shen Rulong R Agrawal Amit A Sukrithan Vineeth V Zhou Ye Y Goyal Ashima A Roll Katie K Shah Manisha M Konda Bhavana B

Case reports in endocrinology 20210522

Immune check point inhibitor (ICI) therapy can be a potentially effective salvage treatment for anaplastic thyroid cancer (ATC) with progression despite standard of care therapies. We report a case of unresectable treatment-naïve ATC showing a dramatic and durable response to first-line pembrolizumab therapy. A 69-year-old male presented with a large, right-sided neck mass associated with compressive symptoms. A neck ultrasound showed a large, right-sided, and highly suspicious thyroid nodule. A ...[more]

PMID: 34123437

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Project description:BackgroundAnaplastic thyroid carcinoma (ATC) is a rare but deadly form of thyroid cancer. Kinase inhibitors kinase inhibitors have shown clinical efficacy in the management of ATC, however, eventually these tumors acquire resistance to KI and patients succumb to their disease. Salvage therapy in this setting is limited. As ATC tumors diffusely express the programmed cell death protein ligand (PD-L1), anti- programmed cell death protein (PD-1) drugs such as pembrolizumab offer therapeutic potential. We sought to explore the efficacy of adding pembrolizumab to kinase inhibitors at progression in ATC.MethodsWe retrospectively reviewed the charts of ATC patients initiated on pembrolizumab in combination with KI at the time of progression on kinase inhibitors at MD Anderson Cancer Center between August 2016 and August 2017. Efficacy was evaluated with best overall response (BOR) using RECISTv1.1 criteria. Progression free survival (PFS) from the start of pembrolizumab and overall survival (OS) from the start of kinase inhibitors, as well as from the time of addition of pembrolizumab were calculated.ResultsTwelve patients were treated with combination kinase inhibitors plus pembrolizumab at the time of progression on their KI therapy. Median age at initiation of pembrolizumab was 60 years (range 47-84 years). BOR was as follows: 5/12 (42%) had partial response, 4/12 (33%) had stable disease and 3/12 (25%) had progressive disease. Median OS from the start of kinase inhibitor was 10.43 months (95% CI = 6.02, 14.83, range 5.4-40 months). Median OS and PFS from the addition of pembrolizumab were 6.93 months (95% CI = 1.7, 12.15, range 3-15.9 months) and 2.96 months (95% CI = 2.2, 3.7, range 0.57-13.14 months), respectively. Fatigue, anemia and hypertension were the most common AEs encountered on these combinations. Therapy had to be discontinued in 2 patients due to drug induced rash and altered mental status likely from progression of disease.ConclusionIn a subset of ATC patients, pembrolizumab may be an effective salvage therapy added to kinase inhibitors at the time of progression on these drugs. However, better treatment strategies aimed at incorporating immunotherapy in patients with ATC should be explored. Frontline combination of KI with immunotherapy should be studied in prospective clinical trials.

Project description:Background: Anaplastic thyroid carcinoma (ATC) and metastatic poorly differentiated thyroid carcinomas (PDTCs) are rare aggressive malignancies with poor overall survival (OS) despite extensive multimodal therapy. These tumors are highly proliferative, with frequently increased tumor mutational burden (TMB) compared with differentiated thyroid carcinomas, and elevated programmed death ligand 1 (PD-L1) levels. These tumor properties implicate responsiveness to antiangiogenic and antiproliferative multikinase inhibitors such as lenvatinib, and immune checkpoint inhibitors such as pembrolizumab. Patients and Methods: In a retrospective study, we analyzed six patients with metastatic ATC and two patients with PDTC, who received a combination therapy of lenvatinib and pembrolizumab. Lenvatinib was started at 14-24 mg daily and combined with pembrolizumab at a fixed dose of 200 mg every three weeks. Maximum treatment duration with this combination was 40 months, and 3 of 6 ATC patients are still on therapy. Patient tumors were characterized by whole-exome sequencing and PD-L1 expression levels (tumor proportion score [TPS] 1-90%). Results: Best overall response (BOR) within ATCs was 66% complete remissions (4/6 CR), 16% stable disease (1/6 SD), and 16% progressive disease (1/6 PD). BOR within PDTCs was partial remission (PR 2/2). The median progression-free survival was 17.75 months for all patients, and 16.5 months for ATCs, with treatment durations ranging from 1 to 40 months (1, 4, 11, 15, 19, 25, 27, and 40 months). Grade III/IV toxicities developed in 4 of 8 patients, requiring dose reduction/discontinuation of lenvatinib. The median OS was 18.5 months, with three ATC patients being still alive without relapse (40, 27, and 19 months) despite metastatic disease at the time of treatment initiation (UICC and stage IVC). All patients with long-term (>2 years) or complete responses (CRs) had either increased TMB or a PD-L1 TPS >50%. Conclusions: Our results implicate that the combination of lenvatinib and pembrolizumab might be safe and effective in patients with ATC/PDTC and can result in complete and long-term remissions. The combination treatment is now being systematically examined in a phase II clinical trial (Anaplastic Thyroid Carcinoma Lenvatinib Pembrolizumab [ATLEP]) in ATC/PDTC patients.

Dataset Information

Pembrolizumab in a Patient with Treatment-Naive Unresectable BRAF-Mutation Negative Anaplastic Thyroid Cancer.

Publications

Pembrolizumab in a Patient with Treatment-Naïve Unresectable BRAF-Mutation Negative Anaplastic Thyroid Cancer.

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