Genomic Correlates of Response to Everolimus in Aggressive Radioiodine-refractory Thyroid Cancer: A Phase II Study
| العنوان: | Genomic Correlates of Response to Everolimus in Aggressive Radioiodine-refractory Thyroid Cancer: A Phase II Study |
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| المؤلفون: | Sewanti Limaye, Antonio Calles, Krystof Misiwkeiwicz, Stefan Kraft, Ellen Marqusee, Anne O'Neill, Glenn J. Hanna, Nicole G. Chau, Robert I. Haddad, Guilherme Rabinowits, Matthew A. Nehs, Lori J. Wirth, Naifa L. Busaidy, Erik K. Alexander, Maria E. Cabanillas, Pasi A. Jänne, Francis D. Moore, Justine A. Barletta, Stephanie L. Lee, Tom Thomas, Jochen H. Lorch |
| المصدر: | Clinical Cancer Research. 24:1546-1553 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Phases of clinical research, Antineoplastic Agents, Thyroid Carcinoma, Anaplastic, Iodine Radioisotopes, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Clinical endpoint, Humans, Medicine, Everolimus, Prospective Studies, Thyroid Neoplasms, Anaplastic thyroid cancer, Adverse effect, Thyroid cancer, PI3K/AKT/mTOR pathway, Aged, Aged, 80 and over, business.industry, Medullary thyroid cancer, Middle Aged, medicine.disease, Carcinoma, Neuroendocrine, 030104 developmental biology, 030220 oncology & carcinogenesis, Female, business, medicine.drug |
| الوصف: | Purpose: Targeting mutations leading to PI3K/mTOR/Akt activation are of interest in thyroid cancer. We evaluated the efficacy of everolimus in aggressive, radioactive iodine–refractory (RAIR) thyroid cancer and correlated tumor mutational profiling with response. Exploratory medullary and anaplastic thyroid cancer cohorts were included. Experimental Design: This single-arm, multi-institutional phase II study was conducted from 2009 to 2013 in patients with incurable RAIR thyroid cancer who had radiographic progression six months prior to enrollment. The primary endpoint was progression-free survival (PFS) with a median follow-up of 31.8 months. The study is closed to enrollment but treatment and follow-up are ongoing. A targeted next-generation sequencing platform was used for mutational analysis. Results: Thirty-three patients with differentiated thyroid cancer (DTC), 10 with medullary thyroid cancer (MTC), and 7 with anaplastic thyroid cancer (ATC) enrolled. For the DTC cohort, median PFS was 12.9 months (95% CI, 7.3–18.5) with a 2-year PFS of 23.6% (95% CI, 10.5–39.5). Median OS was not reached; 2-year OS was 73.5% (95% CI, 53.8–85.8). Among ATC patients, 1 had a partial response and was progression-free until 17.9 months after study entry and one had disease stability for 26 months, respectively. The genomically profiled cohort enriched for PI3K/mTOR/Akt alterations. PI3K/mTOR/Akt–mutated ATC subgroups appeared to benefit from everolimus. Treatment-related adverse events were as anticipated. Conclusions: Everolimus has significant antitumor activity in thyroid cancer. While genomic profiling does not currently guide therapeutic selection in thyroid cancer patients, these data have important implications when considering the use of an mTOR inhibitor in an era of precision medicine. Clin Cancer Res; 24(7); 1546–53. ©2018 AACR. |
| تدمد: | 1557-3265 1078-0432 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8177b55c47508fcf328e978a053b4d77Test https://doi.org/10.1158/1078-0432.ccr-17-2297Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8177b55c47508fcf328e978a053b4d77 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 |
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