Nalysis of PFS was occasion driven, incorporated radiographic progression events per the IRC and deaths, and included all randomly assigned sufferers (ie, the intentiontotreat population). Sufferers who received subsequent anticancer treatment have been censored. Prespecified subgroup analyses and planned sensitivity analyses of PFS are described in the Information Supplement. Safety analyses included sufferers who received at least a single dose of study remedy. For the main finish point of PFS, the study was made to possess 90 power to detect an HR of 0.571 utilizing the logrank test plus a twosided significance level of five . This corresponds to a 43 reduction in the danger of progression or death or maybe a 75 improvement in median PFS from eight months to 14 months. In all, 138 progression events have been needed, and 315 individuals have been planned for enrollment. Consequently, all patients except the first 138 to knowledge an event were censored in the PFS analysis, contributing timetoevent information till the date of censoring. Statistical considerations for the end point of OS are described inside the Data Supplement. Statistical analysis was performed independently by the sponsor.RESULTSPatients From September 2008 via February 2011, 330 individuals from 23 nations had been randomly assigned two:1 to acquire cabozantinib (219 sufferers) or placebo (111 sufferers; Fig 1). Baseline characteristics within the remedy groups had been nicely balanced (Table 1). Forty percent of patients (n 133) had received prior anticancer therapy, and 21 (n 68) received prior TKI therapy. Twentyfive percent had two or a lot more systemic therapies (24 cabozantinb; 28 placebo). Most patients (285 [86 ]) had sporadic illness. Approximately half the individuals (48.two ; n 159) have been RET mutation ositive, 12 (n 41) have been RET mutation egative, and 39 (n 130) had unknown RET mutation status on account of missing sequence data or towards the presence of a mutation of unknown significance. M918T was the predominant RET mutation (74 ; 118 of 159 sufferers with documented mutations). The key websites of illness within the majority of patients included lymph nodes, liver, lung, and bone. Treatment At the database cutoff date, 45 (98 of 219) of sufferers inside the cabozantinib arm and 14 (15 of 111) of patients within the placebo arm have been getting study remedy.Silver(I) carbonate Purity The arithmetic median duration of exposure was 204 days for cabozantinibtreated patients (interquartile range, 99 to 392 days), virtually twice that of placebotreated sufferers (median 105 days; interquartile range, 83 to 170 days).Triphenylbismuth site As a result of the big percentage of individuals getting therapy at information cutoff, the median duration of exposure is definitely an underestimate within the cabozantinib therapy group.PMID:23937941 The median time of followup was 13.9 months (range, three.6 to 32.5 months). PFS The study met its primary end point of demonstrating improvement in PFS as determined by the IRC (Fig 2A). Cabozantinib treatment led to a substantial improvement in PFS compared with placebo.JOURNAL OF CLINICAL ONCOLOGYCabozantinib in Progressive Medullary Thyroid CancerAssessed for eligibility (N = 548) Not randomly assigned Did not meet eligibility criteria Voluntary discontinuation Randomly assigned (two:1) (n = 330) Assigned to cabozantinib arm Continued remedy Discontinued treatment Didn’t receive remedy PD AE Death Participant request Investigator selection Other Included in ITT population Incorporated in security population (n = 219) 45 55 2 26 16 five 4 1 1 (n = 219) (n = 214) Assigned to placebo arm Continued treatm.