Priyanka C Iyer1,2, Ramona Dadu1, Renata Ferrarotto3, Naifa L Busaidy1, Mouhammed A Habra1, Mark Zafereo4, Neil Gross4, Kenneth R Hess5, Maria Gule-Monroe6, Michelle D Williams7, Maria E Cabanillas1. 1. 1 Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center , Houston, Texas. 2. 2 Department of Endocrinology, Diabetes and Metabolism, Baylor College of Medicine , Houston, Texas. 3. 3 Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center , Houston, Texas. 4. 4 Department of Head and Neck Surgery, Division of Surgery, The University of Texas MD Anderson Cancer Center , Houston, Texas. 5. 5 Department of Biostatistics, The University of Texas MD Anderson Cancer Center , Houston, Texas. 6. 6 Department of Diagnostic Radiology, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center , Houston, Texas. 7. 7 Department of Pathology, Division of Pathology/Lab Medicine, The University of Texas MD Anderson Cancer Center , Houston, Texas.
Abstract
BACKGROUND: Patients with anaplastic thyroid cancer (ATC) have a dismal prognosis, despite systemic cytotoxic chemotherapy. The objective of this study was to investigate the efficacy and safety of targeted therapy in ATC patients when used outside of a clinical trial. METHODS: This is a retrospective review from April 2015 to May 2016 at a single academic institution where 16 ATC patients receiving targeted therapy outside of a clinical trial were studied. Ten patients (eight BRAF wild type and two BRAFV600E mutant tumors) were started on lenvatinib, and six with BRAFV600E-mutated tumors received a combination of dabrafenib plus trametinib. Best response evaluated by RECIST v1.1, progression-free survival, and overall survival were determined. Adverse events were evaluated for safety. RESULTS: The majority of patients (63%) were men, and all had distant metastases or radiation-resistant primary disease at the time of treatment. In the entire cohort, 6/16 (38%) had a partial response, 6/16 (38%) had stable disease, and 2/16 (12%) had progressive disease. Two (12%) patients died before restaging. Median follow-up time was 11.8 months. Median progression-free survival was 3.7 months [confidence interval 1.8-7.6] in the entire cohort, 2.7 months for lenvatinib, and 5.2 months for dabrafenib plus trametinib. Median OS was 6.3 months [confidence interval 1.8-7.6] for the entire cohort, 3.9 months for lenvatinib, and 9.3 months for dabrafenib plus trametinib. Adverse events were as expected and manageable. CONCLUSIONS: Targeted therapies, lenvatinib, and dabrafenib plus trametinib (for BRAFV600E mutants) may provide clinical benefit in ATC patients who are unable to participate in clinical trials, and toxicities are manageable.
BACKGROUND:Patients with anaplastic thyroid cancer (ATC) have a dismal prognosis, despite systemic cytotoxic chemotherapy. The objective of this study was to investigate the efficacy and safety of targeted therapy in ATC patients when used outside of a clinical trial. METHODS: This is a retrospective review from April 2015 to May 2016 at a single academic institution where 16 ATC patients receiving targeted therapy outside of a clinical trial were studied. Ten patients (eight BRAF wild type and two BRAFV600E mutant tumors) were started on lenvatinib, and six with BRAFV600E-mutated tumors received a combination of dabrafenib plus trametinib. Best response evaluated by RECIST v1.1, progression-free survival, and overall survival were determined. Adverse events were evaluated for safety. RESULTS: The majority of patients (63%) were men, and all had distant metastases or radiation-resistant primary disease at the time of treatment. In the entire cohort, 6/16 (38%) had a partial response, 6/16 (38%) had stable disease, and 2/16 (12%) had progressive disease. Two (12%) patients died before restaging. Median follow-up time was 11.8 months. Median progression-free survival was 3.7 months [confidence interval 1.8-7.6] in the entire cohort, 2.7 months for lenvatinib, and 5.2 months for dabrafenib plus trametinib. Median OS was 6.3 months [confidence interval 1.8-7.6] for the entire cohort, 3.9 months for lenvatinib, and 9.3 months for dabrafenib plus trametinib. Adverse events were as expected and manageable. CONCLUSIONS: Targeted therapies, lenvatinib, and dabrafenib plus trametinib (for BRAFV600E mutants) may provide clinical benefit in ATC patients who are unable to participate in clinical trials, and toxicities are manageable.
Authors: Kristen Wong; Francesca Di Cristofano; Michela Ranieri; Daniela De Martino; Antonio Di Cristofano Journal: Endocr Relat Cancer Date: 2019-01-01 Impact factor: 5.678
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Authors: Keith C Bible; Electron Kebebew; James Brierley; Juan P Brito; Maria E Cabanillas; Thomas J Clark; Antonio Di Cristofano; Robert Foote; Thomas Giordano; Jan Kasperbauer; Kate Newbold; Yuri E Nikiforov; Gregory Randolph; M Sara Rosenthal; Anna M Sawka; Manisha Shah; Ashok Shaha; Robert Smallridge; Carol K Wong-Clark Journal: Thyroid Date: 2021-03 Impact factor: 6.568