Salvage pembrolizumab added to kinase inhibitor therapy for the treatment of anaplastic thyroid carcinoma
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...
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| Published in | Journal for immunotherapy of cancer Vol. 6; no. 1; pp. 68 - 10 |
|---|---|
| Main Authors | , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
BioMed Central Ltd
11.07.2018
BMJ Publishing Group LTD BioMed Central BMJ Publishing Group |
| Subjects | |
| Online Access | Get full text |
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| Abstract | 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.
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.
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.
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. |
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| AbstractList | 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, Immunotherapy, Salvage, Thyroid cancer, Lenvatinib, Dabrafenib, Trametinib, Undifferentiated 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. |
| ArticleNumber | 68 |
| Audience | Academic |
| Author | Sturgis, Erich M Habra, Mouhammed Amir Grosu, Horiana Dadu, Ramona Ferrarotto, Renata Gross, Neil Zafereo, Mark Iyer, Priyanka C Gunn, G Brandon Cabanillas, Maria E Gule-Monroe, Maria Skinner, Heath D Busaidy, Naifa L Williams, Michelle D |
| Author_xml | – sequence: 1 givenname: Priyanka C surname: Iyer fullname: Iyer, Priyanka C organization: Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1461, Houston, TX, 77030, USA – sequence: 2 givenname: Ramona surname: Dadu fullname: Dadu, Ramona organization: Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1461, Houston, TX, 77030, USA – sequence: 3 givenname: Maria surname: Gule-Monroe fullname: Gule-Monroe, Maria organization: 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 – sequence: 4 givenname: Naifa L surname: Busaidy fullname: Busaidy, Naifa L organization: Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1461, Houston, TX, 77030, USA – sequence: 5 givenname: Renata surname: Ferrarotto fullname: Ferrarotto, Renata organization: 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 – sequence: 6 givenname: Mouhammed Amir surname: Habra fullname: Habra, Mouhammed Amir organization: Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1461, Houston, TX, 77030, USA – sequence: 7 givenname: Mark surname: Zafereo fullname: Zafereo, Mark organization: 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 – sequence: 8 givenname: Michelle D surname: Williams fullname: Williams, Michelle D organization: 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 – sequence: 9 givenname: G Brandon surname: Gunn fullname: Gunn, G Brandon organization: Department of Radiation Oncology, Division of Radiation Oncology, Proton Therapy Center, 1515 Holcombe Blvd, Unit 0097, Houston, TX, USA – sequence: 10 givenname: Horiana surname: Grosu fullname: Grosu, Horiana organization: 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 – sequence: 11 givenname: Heath D surname: Skinner fullname: Skinner, Heath D organization: Department of Radiation Oncology, Division of Radiation Oncology, Proton Therapy Center, 1515 Holcombe Blvd, Unit 0097, Houston, TX, USA – sequence: 12 givenname: Erich M surname: Sturgis fullname: Sturgis, Erich M organization: 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 – sequence: 13 givenname: Neil surname: Gross fullname: Gross, Neil organization: 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 – sequence: 14 givenname: Maria E surname: Cabanillas fullname: Cabanillas, Maria E email: mcabani@mdanderson.org organization: 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 |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29996921$$D View this record in MEDLINE/PubMed |
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| ContentType | Journal Article |
| Copyright | COPYRIGHT 2018 BioMed Central Ltd. 2018 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. The Author(s). 2018 |
| Copyright_xml | – notice: COPYRIGHT 2018 BioMed Central Ltd. – notice: 2018 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: The Author(s). 2018 |
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| DOI | 10.1186/s40425-018-0378-y |
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| Keywords | Anaplastic thyroid cancer Salvage Thyroid cancer Immunotherapy Undifferentiated Dabrafenib Lenvatinib Trametinib |
| Language | English |
| License | Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
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| References | 378_CR3 378_CR24 I Landa (378_CR1) 2016; 126 ME Cabanillas (378_CR15) 2016; 3 378_CR26 E Brauner (378_CR19) 2016; 7 N Denaro (378_CR27) 2013; 9 RC Smallridge (378_CR2) 2010; 22 AA Carhill (378_CR29) 2013; 98 IB Barsoum (378_CR36) 2014; 74 378_CR8 SA Forbes (378_CR14) 2015; 43 BP Danysh (378_CR18) 2016; 7 NM Iniguez-Ariza (378_CR30) 2017; 27 BR Haugen (378_CR31) 2016; 26 I Sugitani (378_CR6) 2014; 36 M Tahara (378_CR9) 2017; 7 JW Kunstman (378_CR12) 2015; 24 378_CR17 R Dadu (378_CR23) 2015; 25 KG Liu (378_CR35) 2017; 8 378_CR37 PC Iyer (378_CR11) 2018; 28 AV Chintakuntlawar (378_CR21) 2017; 102 EJ Sherman (378_CR5) 2011; 101 S Latteyer (378_CR13) 2016; 54 KSA KP (378_CR25) 2018 SJ Shin (378_CR20) 2015; 20 A Amin (378_CR38) 2014; 32 JJ Bastman (378_CR22) 2016; 101 RA Szczepaniak Sloane (378_CR34) 2017; 123 ME Cabanillas (378_CR16) 2016; 12 DM Hyman (378_CR10) 2015; 373 J Tennvall (378_CR4) 2002; 86 RL Foote (378_CR7) 2011; 21 378_CR28 R Kollipara (378_CR32) 2017; 22 MB Atkins (378_CR33) 2016; 108 |
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| Snippet | Anaplastic thyroid carcinoma (ATC) is a rare but deadly form of thyroid cancer. Kinase inhibitors kinase inhibitors have shown clinical efficacy in the... Background Anaplastic thyroid carcinoma (ATC) is a rare but deadly form of thyroid cancer. Kinase inhibitors kinase inhibitors have shown clinical efficacy in... BackgroundAnaplastic thyroid carcinoma (ATC) is a rare but deadly form of thyroid cancer. Kinase inhibitors kinase inhibitors have shown clinical efficacy in... Abstract Background Anaplastic thyroid carcinoma (ATC) is a rare but deadly form of thyroid cancer. Kinase inhibitors kinase inhibitors have shown clinical... |
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| SubjectTerms | Aged Aged, 80 and over Anaplastic thyroid cancer Antibodies, Monoclonal, Humanized - administration & dosage Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - therapeutic use Apoptosis Cancer Cancer therapies Cancer treatment Carcinoma Chemotherapy Dabrafenib Development and progression Drug therapy FDA approval Female Genomics Health aspects Humans Immunotherapy Lenvatinib Male Medical research Metastasis Middle Aged Monoclonal antibodies Mutation Patients Protein Kinase Inhibitors - administration & dosage Radiation Retrospective Studies Salvage Salvage Therapy Surgery Targeted cancer therapy Thyroid cancer Thyroid Carcinoma, Anaplastic - drug therapy Thyroid Carcinoma, Anaplastic - metabolism Thyroid Carcinoma, Anaplastic - pathology Thyroid Neoplasms - drug therapy Thyroid Neoplasms - metabolism Thyroid Neoplasms - pathology Treatment Outcome Tumors |
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| Title | Salvage pembrolizumab added to kinase inhibitor therapy for the treatment of anaplastic thyroid carcinoma |
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