Reference Detail

Ref Type Journal Article
PMID (29301825)
Authors Hanna GJ, Busaidy NL, Chau NG, Wirth LJ, Barletta JA, Calles A, Haddad RI, Kraft S, Cabanillas ME, Rabinowits G, O'Neill A, Limaye SA, Alexander EK, Moore FD, Misiwkeiwicz K, Thomas T, Nehs M, Marqusee E, Lee SL, Jänne PA, Lorch JH
Title Genomic Correlates of Response to Everolimus in Aggressive Radioiodine-refractory Thyroid Cancer: A Phase II Study.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 24
Issue 7
Date 2018 Apr 01
URL
Abstract Text 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown thyroid cancer not applicable Everolimus Phase II Actionable In a Phase II trial, treatment with Afinitor (everolimus) resulted in a median progression-free survival (PFS) of 12.9 months, 2-year PFS of 23.6%, and 2-year overall survival of 73.5% in patients with differentiated thyroid cancer, and a partial response in a patient with anaplastic thyroid cancer (ATC), and disease stability for 26 months in another ATC patient (PMID: 29301825). 29301825