scholarly journals Long-term analysis of the efficacy and tolerability of sorafenib in advanced radio-iodine refractory differentiated thyroid carcinoma: final results of a phase II trial

2012 ◽  
Vol 167 (5) ◽  
pp. 643-650 ◽  
Author(s):  
T C Schneider ◽  
R M Abdulrahman ◽  
E P Corssmit ◽  
H Morreau ◽  
J W A Smit ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Phase Ii ◽  
Differentiated Thyroid Cancer ◽  
Locally Advanced ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Differentiated Thyroid Carcinoma ◽  
Long Term Results ◽  
Best Response

Objective We conducted a prospective phase II clinical trial to determine the efficacy of sorafenib in patients with advanced radio-iodine refractory differentiated thyroid cancer. In this article, the long-term results are presented. Patients and methods Thirty-one patients with progressive metastatic or locally advanced radioactive iodine refractory differentiated thyroid cancer received sorafenib 400 mg orally twice daily. The study end points included response rate, progression-free survival (PFS), overall survival (OS), best response by Response Evaluation Criteria in Solid Tumors criteria 1.0, and toxicity. Results Median PFS was 18 months (95% confidence interval (95% CI): 7–29 months) and median OS was 34.5 months (95% CI: 19–50 months). Eight patients (31%) achieved a partial response and 11 patients (42%) showed stable disease after a median follow-up of 25 months (range 3.5–39 months). Toxicity mostly included hand foot syndrome, weight loss, diarrhea, and rash. Conclusion Sorafenib has clinically relevant antitumor activity in patients with progressive metastatic or locally advanced radio-iodine refractory differentiated thyroid cancer. Sorafenib can nowadays be considered as the standard option in these patients.

scholarly journals Cabozantinib As Salvage Therapy for Patients With Tyrosine Kinase Inhibitor–Refractory Differentiated Thyroid Cancer: Results of a Multicenter Phase II International Thyroid Oncology Group Trial

2017 ◽  
Vol 35 (29) ◽  
pp. 3315-3321 ◽  
Author(s):  
Maria E. Cabanillas ◽  
Jonas A. de Souza ◽  
Susan Geyer ◽  
Lori J. Wirth ◽  
Michael E. Menefee ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Targeted Therapy ◽  
Phase Ii ◽  
Differentiated Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Multikinase Inhibitor

Purpose Sorafenib and lenvatinib are oral multikinase inhibitors targeting vascular endothelial growth factor receptor (VEGFR) and approved for radioiodine (RAI)-refractory differentiated thyroid cancer (DTC). However, there are no approved second- or third-line therapies. MET is implicated in resistance to VEGFR inhibitors. Cabozantinib is an oral multikinase inhibitor targeting MET in addition to VEGFR and is approved for medullary thyroid cancer. In a phase I study of cabozantinib, five of eight patients with DTC previously treated with a VEGFR-targeted therapy had an objective response to cabozantinib. Patients and Methods Patients with RAI-refractory disease with Response Evaluation Criteria in Solid Tumor (RECIST) measurable disease and evidence of progression on prior VEGFR-targeted therapy were enrolled in this single-arm phase II study. The cabozantinib starting dose was 60 mg/day orally but could be escalated to 80 mg if the patient did not experience a response. Patients underwent tumor assessment according to RECIST v1.1 every 8 weeks. In this study, if at least five of 25 response-evaluable patients had an objective response, cabozantinib would be considered a promising agent in this patient population. Results Twenty-five patients were enrolled. The median age was 64 years, and 64% of patients were men. Twenty-one patients had received only one prior VEGFR-targeted therapy (sorafenib, pazopanib, or cediranib), and four patients had received two such therapies. The most common treatment-related adverse events were fatigue, weight loss, diarrhea, palmar-plantar erythrodysesthesia, and hypertension. One drug-related death was noted. Of the 25 patients, 10 (40%) had a partial response, 13 (52%) had stable disease, and two (8%) had nonevaluable disease. The median progression-free survival and overall survival were 12.7 months and 34.7 months, respectively. Conclusion Cabozantinib demonstrated clinically significant, durable objective response activity in patients with RAI-refractory DTC who experienced disease progression while taking prior VEGFR-targeted therapy.

Long-term results of phase II trial of apatinib for progressive radioiodine refractory differentiated thyroid cancer

2021 ◽  
Author(s):  
Yan-Song Lin ◽  
Xin Zhang ◽  
Chen Wang ◽  
Yan-Qing Liu ◽  
Wen-Min Guan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Thyroid Cancer ◽  
Phase Ii ◽  
Differentiated Thyroid Cancer ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Phase Ii Clinical Trial ◽  
Braf V600e ◽  
Long Term Results

Abstract Context Radioiodine refractory differentiated thyroid cancer (RAIR-DTC) has been a global challenge due to its poor prognosis and limited treatment options. Objective To report the long-term results of the phase II clinical trial of apatinib, an anti-angiogenic tyrosine kinase inhibitor, for RAIR-DTC. Design, Setting, Participants Open-label, exploratory phase II clinical trial among progressive RAIR-DTC patients. Intervention Apatinib treatment once daily until disease progression, unmanageable toxicity, withdrawal, or death. Main Outcome Measures The primary end points were objective response rate (ORR) and disease control rate (DCR). Progression-free survival (PFS), overall survival (OS), duration of response, long-term safety and the association between patients with different tumor genotype (BRAF  V600E and TERT promotor mutation) and their PFS were also assessed. Results The ORR was 80%, and the DCR was 95%. The overall median PFS was 18.4 months (95% confidence interval [CI], 9.2-36.8 months) and median OS was 51.6 months (95%CI, 29.2-not reached [NR]). Patients with BRAF  V600E mutation (10 of 18 evaluated) had a longer median PFS compared with patients with BRAF wild-type (NR vs. 9.2 months, P=0.002). The most common adverse events included palmar-plantar erythrodysaesthesia syndrome (19/20), proteinuria (18/20) and hypertension (16/20). Conclusions In this long-term evaluation, apatinib displayed sustainable efficacy and tolerable safety profile, warranting it as a promising treatment option for progressive RAIR-DTC.

OC-0210 Long-term results from the phase II/III Act.In.Sarc trial evaluating NBTXR3 in locally advanced STS

2021 ◽  
Vol 161 ◽  
pp. S142
Author(s):  
S. Bonvalot ◽  
P. Rutkowski ◽  
J. Thariat ◽  
S. Carrère ◽  
A. Ducassou ◽  
...  
Keyword(s):  
Phase Ii ◽  
Locally Advanced ◽  
Long Term Results

scholarly journals Does the Addition of Cetuximab to Radiochemotherapy Improve Outcome of Patients with Locally Advanced Rectal Cancer? Long-Term Results from Phase II Trials

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
M. Kripp ◽  
K. Horisberger ◽  
S. Mai ◽  
P. Kienle ◽  
T. Gaiser ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Long Term Results ◽  
Phase Ii Trials ◽  
Exon 2 ◽  
Significant Difference

Purpose. The addition of cetuximab to radiochemotherapy (RCT) failed to improve complete response rates in locally advanced rectal cancer (LARC). We report the long-term results in patients treated within two sequential clinical trials.Methods. Patients receiving neoadjuvant RCT using capecitabine and irinotecan (CapIri) within a phase I/II trial or CapIri + cetuximab within a phase II trial were evaluated for analysis of disease-free survival (DFS) and overall survival (OS). KRAS exon 2 mutational status had been analyzed in patients receiving cetuximab.Results. 37 patients from the CapIri trial and 49 patients from the CapIri-cetuximab treatment group were evaluable. Median follow-up time was 75.2 months. The 5-year DFS rate was 82% (CapIri) and 79% (CapIri-cetuximab)(P=0.62). The median OS was 127.4 months. 5-year OS was 73% for both groups (CapIri and CapIri-cetuximab)(P=0.61). No significant difference in DFS(P=0.86)or OS(P=0.39)was noticed between patients receiving CapIri and those receiving CapIri-cetuximab with KRAS wild-type tumors.Conclusions. As the addition of cetuximab did not improve neither DFS nor OS it should not play a role in the perioperative treatment of patients with LARC, not even of patients with (K)RAS WT tumors.

scholarly journals Analysis of the efficacy and toxicity of sorafenib in thyroid cancer: a phase II study in a UK based population

2011 ◽  
Vol 165 (2) ◽  
pp. 315-322 ◽  
Author(s):  
Merina Ahmed ◽  
Yolanda Barbachano ◽  
Angela Riddell ◽  
Jen Hickey ◽  
Katie L Newbold ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Differentiated Thyroid Carcinoma ◽  
Free Survival ◽  
Hand Foot Syndrome ◽  
Secondary Endpoints ◽  
Radiological Response ◽  
Dose Reductions

AimTo evaluate the tolerability and efficacy of sorafenib in patients with thyroid carcinoma.MethodsPatients with progressive locally advanced/metastatic medullary thyroid carcinoma (MTC), or differentiated thyroid carcinoma (DTC) with non-radioiodine-avid disease, were treated with sorafenib 400 mg twice daily until disease progression. The primary endpoint was the radiological response rate (RR) at 6 months. Secondary endpoints were RR at 3, 9 and 12 months, biochemical responses, toxicity, biomarker analyses and progression free and overall survival (OS).ResultsA total of 34 patients were recruited to the study (15 medullary and 19 differentiated). After 6 months, the RR rate was 15% and a further 74% of patients achieved stable disease in the first 6 months. After 12 months of treatment, the RR was 21%. In the MTC patients, the RR at 12 months was 25% and OS was 100%. In DTC patients corresponding rates were 18 and 79% respectively. Median overall and progression-free survival points were not reached at 19 months. Commonest adverse events included hand–foot syndrome, other skin toxicities, diarrhoea and alopecia. Dose reduction was required in 79% patients. Median time on treatment was 16.5 months.ConclusionThis study demonstrates that sorafenib is tolerable at reduced doses over prolonged periods of time in patients with thyroid cancer. Sorafenib leads to radiological and biochemical stabilisation of disease in the majority of these patients despite dose reductions.

scholarly journals Axitinib Is an Active Treatment for All Histologic Subtypes of Advanced Thyroid Cancer: Results From a Phase II Study

2008 ◽  
Vol 26 (29) ◽  
pp. 4708-4713 ◽  
Author(s):  
Ezra E.W. Cohen ◽  
Lee S. Rosen ◽  
Everett E. Vokes ◽  
Merrill S. Kies ◽  
Arlene A. Forastiere ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Phase Ii ◽  
Objective Response ◽  
Plasma Concentrations ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Selective Inhibitor ◽  
Duration Of Response ◽  
Advanced Thyroid Cancer ◽  
Histologic Subtypes

PurposePatients with advanced, incurable thyroid cancer not amenable to surgery or radioactive iodine (131I) therapy have few satisfactory therapeutic options. This multi-institutional study assessed the activity and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 in patients with advanced thyroid cancer.Patients and MethodsPatients with thyroid cancer of any histology that was resistant or not appropriate for131I were enrolled onto a single-arm phase II trial to receive axitinib orally (starting dose, 5 mg twice daily). Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors was the primary end point. Secondary end points included duration of response, progression-free survival (PFS), overall survival, safety, and modulation of soluble (s) VEGFR.ResultsSixty patients were enrolled. Partial responses were observed in 18 patients, yielding an ORR of 30% (95% CI, 18.9 to 43.2). Stable disease lasting ≥ 16 weeks was reported in another 23 patients (38%). Objective responses were noted in all histologic subtypes. Median PFS was 18.1 months (95% CI, 12.1 to not estimable). Axitinib was generally well tolerated, with the most common grade ≥ 3 treatment-related adverse event being hypertension (n = 7; 12%). Eight patients (13%) discontinued treatment because of adverse events. Axitinib selectively decreased sVEGFR-2 and sVEGFR-3 plasma concentrations versus sKIT, demonstrating its targeting of VEGFR.ConclusionAxitinib is a selective inhibitor of VEGFR with compelling antitumor activity in all histologic subtypes of advanced thyroid cancer.

Sign in / Sign up

Export Citation Format

Share Document