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J Immunother Cancer. 2018 Jul 11;6(1):68. doi: 10.1186/s40425-018-0378-y.

Salvage pembrolizumab added to kinase inhibitor therapy for the treatment of anaplastic thyroid carcinoma.

Author information

1
Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1461, Houston, TX, 77030, USA.
2
Department of Diagnostic Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1482, Houston, TX, 77030, USA.
3
Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0432, Houston, TX, 77030, USA.
4
Department of Head and Neck Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1445, Houston, TX, 77030, USA.
5
Department of Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 0085, Houston, TX, 77030, USA.
6
Department of Radiation Oncology, Division of Radiation Oncology, Proton Therapy Center, 1515 Holcombe Blvd, Unit 0097, Houston, TX, USA.
7
Department of Pulmonary Medicine, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1462, Houston, TX, 77030, USA.
8
Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1461, Houston, TX, 77030, USA. mcabani@mdanderson.org.

Abstract

BACKGROUND:

Anaplastic 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.

METHODS:

We 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.

RESULTS:

Twelve 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.

CONCLUSION:

In 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.

KEYWORDS:

Anaplastic thyroid cancer; Dabrafenib; Immunotherapy; Lenvatinib; Salvage; Thyroid cancer; Trametinib; Undifferentiated

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