***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: This analysis was performed to determine the effect of initial therapy on the outcomes of thyroid cancer patients . The study setting was a prospect ively followed multi-institutional registry . Patients were stratified as low risk ( stages I and II ) or high risk ( stages III and IV ) . Treatments employed included near-total thyroidectomy , administration of radioactive iodine , and thyroid hormone suppression therapy . Outcome measures were overall survival , disease-specific survival , and disease-free survival .  Near-total thyroidectomy , radioactive iodine , and aggressive thyroid hormone suppression therapy were each independently associated with longer overall survival in high-risk patients . Near-total thyroidectomy followed by radioactive iodine therapy , and moderate thyroid hormone suppression therapy , both predicted improved overall survival in stage II patients . No treatment modality , including lack of radioactive iodine , was associated with altered survival in stage I patients . Based on our overall survival data , we confirm that near-total thyroidectomy is indicated in high-risk patients . We also conclude that radioactive iodine therapy is beneficial for stage II , III , and IV patients . Importantly , we show for the first time that superior outcomes are associated with aggressive thyroid hormone suppression therapy in high-risk patients , but are achieved with modest suppression in stage II patients . We were unable to show any impact , positive or negative , of specific therapies in stage I patients Lenvatinib is an oral , multitargeted tyrosine kinase inhibitor of the vascular endothelial growth factor receptors 1 through 3 ( VEGFR1‐VEGFR3 ) , fibroblast growth factor receptors 1 through 4 ( FGFR1‐FGFR4 ) , platelet‐derived growth factor receptor α ( PDGFRα ) , ret proto‐oncogene ( RET ) , and v‐kit Hardy‐Zuckerman 4 feline sarcoma viral oncogene homolog ( KIT ) signaling networks implicated in tumor angiogenesis . Positive phase 1 results in solid tumors prompted a phase 2 trial in patients with advanced , radioiodine‐refractory , differentiated thyroid cancer ( RR‐DTC ) . Effective adverse event ( AE ) management is critical to maintaining patients on anticancer therapies . The DECISION trial was a multicenter , r and omized , double-blind , placebo-controlled , Phase 3 trial which investigated sorafenib for treatment of progressive , advanced , or metastatic radioactive iodine-refractory , differentiated thyroid carcinoma . Four hundred and seventeen adult patients were r and omized ( 1:1 ) to receive oral sorafenib ( 400 mg , twice daily ) or placebo , until progression , unacceptable toxicity , noncompliance , or withdrawal . Progression-free survival , the primary endpoint of DECISION , was reported previously . To eluci date the patterns and management of AEs in sorafenib-treated patients in the DECISION trial , this report describes detailed , by-treatment-cycle analyses of the incidence , prevalence , and severity of h and –foot skin reaction ( HFSR ) , rash/desquamation , hypertension , diarrhea , fatigue , weight loss , increased serum thyroid stimulating hormone , and hypocalcemia , as well as the interventions used to manage these AEs . By-cycle incidence of the above-selected AEs with sorafenib was generally highest in cycle 1 or 2 then decreased . AE prevalence generally increased over cycles 2–6 then stabilized or declined . Among these AEs , only weight loss tended to increase in severity ( from grade 1 to 2 ) over time ; severity of HFSR and rash/desquamation declined over time . AEs were mostly grade 1 or 2 , and were generally managed with dose interruptions/reductions , and concomitant medications ( e.g. antidiarrheals , antihypertensives , dermatologic preparations ) . Most dose interruptions/reductions occurred in early cycles . In conclusion , AEs with sorafenib in DECISION were typically grade 1 or 2 , occurred early during the treatment course , and were manageable over time PURPOSE Given the molecular pathophysiology of thyroid cancer and the spectrum of kinases inhibited by sorafenib , including Raf kinase , vascular endothelial growth factor receptors , platelet-derived growth factor receptor , and RET tyrosine kinases , we conducted an open-label phase II trial to determine the efficacy of sorafenib in patients with advanced thyroid carcinoma . PATIENTS AND METHODS Eligible patients with metastatic , iodine-refractory thyroid carcinoma received sorafenib 400 mg orally twice daily . Responses were measured radiographically every 2 to 3 months . The study end points included response rate , progression-free survival ( PFS ) , and best response by Response Evaluation Criteria in Solid Tumors . RESULTS Thirty patients were entered onto the study and treated for a minimum of 16 weeks . Seven patients ( 23 % ; 95 % CI , 0.10 to 0.42 ) had a partial response lasting 18 + to 84 weeks . Sixteen patients ( 53 % ; 95 % CI , 0.34 to 0.72 ) had stable disease lasting 14 to 89 + weeks . Seventeen ( 95 % ) of 19 patients for whom serial thyroglobulin levels were available showed a marked and rapid response in thyroglobulin levels with a mean decrease of 70 % . The median PFS was 79 weeks . Toxicity was consistent with other sorafenib trials , although a single patient died of liver failure that was likely treatment related . CONCLUSION Sorafenib has clinical ly relevant antitumor activity in patients with metastatic , iodine-refractory thyroid carcinoma , with an overall clinical benefit rate ( partial response + stable disease ) of 77 % , median PFS of 79 weeks , and an overall acceptable safety profile . These results represent a significant advance over chemotherapy in both response rate and PFS and support further investigation of this agent in these patients OBJECTIVE We conducted a prospect i ve 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 h and foot syndrome , weight loss , diarrhea , and rash . CONCLUSION Sorafenib has clinical ly relevant antitumor activity in patients with progressive metastatic or locally advanced radio-iodine refractory differentiated thyroid cancer .  Sorafenib can nowadays be considered as the st and ard option in these patients AIM To evaluate the tolerability and efficacy of sorafenib in patients with thyroid carcinoma . METHODS Patients 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 ) . RESULTS A 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 h and -foot syndrome , other skin toxicities , diarrhoea and alopecia . Dose reduction was required in 79 % patients . Median time on treatment was 16.5 months . CONCLUSION This 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 BACKGROUND Lenvatinib , an oral inhibitor of vascular endothelial growth factor receptors 1 , 2 , and 3 , fibroblast growth factor receptors 1 through 4 , platelet-derived growth factor receptor α , RET , and KIT , showed clinical activity in a phase 2 study involving patients with differentiated thyroid cancer that was refractory to radioiodine ( iodine-131 ) . METHODS In our phase 3 , r and omized , double-blind , multicenter study involving patients with progressive thyroid cancer that was refractory to iodine-131  , we r and omly assigned 261 patients to receive lenvatinib ( at a daily dose of 24 mg per day in 28-day cycles ) and 131 patients to receive placebo .  At the time of disease progression , patients in the placebo group could receive open-label lenvatinib . The primary end point was progression-free survival . Secondary end points included the response rate , overall survival , and safety . RESULTS The median progression-free survival was 18.3 months in the lenvatinib group and 3.6 months in the placebo group ( hazard ratio for progression or death , 0.21 ; 99 % confidence interval , 0.14 to 0.31 ; P<0.001 ) . A progression-free survival benefit associated with lenvatinib was observed in all prespecified subgroups . The response rate was 64.8 % in the lenvatinib group ( 4 complete responses and 165 partial responses ) and 1.5 % in the placebo group ( P<0.001 ) . The median overall survival was not reached in either group . Treatment-related adverse effects of any grade , which occurred in more than 40 % of patients in the lenvatinib group , were hypertension ( in 67.8 % of the patients ) , diarrhea ( in 59.4 % ) , fatigue or asthenia ( in 59.0 % ) , decreased appetite ( in 50.2 % ) , decreased weight ( in 46.4 % ) , and nausea ( in 41.0 % ) . Discontinuations of the study drug because of adverse effects occurred in 37 patients who received lenvatinib ( 14.2 % ) and 3 patients who received placebo ( 2.3 % ) . In the lenvatinib group , 6 of 20 deaths that occurred during the treatment period were considered to be drug-related . CONCLUSIONS Lenvatinib , as compared with placebo , was associated with significant improvements in progression-free survival and the response rate among patients with iodine-131-refractory thyroid cancer . Patients who received lenvatinib had more adverse effects . ( Funded by Eisai ; SELECT Clinical Trials.gov number , NCT01321554 . ) 
    Output:
    
Compared to placebo , RCT evidence demonstrated improvements with lenvatinib or sorafenib  in median progression-free survival ( PFS ) and objective tumour response rate ( ORR ) .
Adverse events ( AEs ) were more common with lenvatinib or sorafenib than with placebo but the most common AEs associated with each drug differed .
ORR and AE findings for lenvatinib and sorafenib from the supporting evidence were broadly in line with RCT evidence .
Lenvatinib and sorafenib are more efficacious  than placebo ( a proxy for best supportive care ) for treating RR-DTC .
Uncertainty surrounds the extent of the impact on OS and HRQoL. Lenvatinib could not reliably be compared with sorafenib .