A Number Of Challenging But Also Creative Volasertib Blueprints

The study co-primary endpoints were PFS assessed by the investigator and OS in the intention to treat population. Patients were randomly assigned in a 2:1 ratio to treatment with T-DM1 at 3.6 mg/kg every 21 days or treatment of physician��s choice that was restricted to single-agent, approved chemotherapy; single-agent or combined HER2-directed therapy; combination of chemotherapy and HER2-directed therapy; or hormonal therapy for hormone receptor-positive disease. Patients continued treatment until disease progression or unmanageable toxicity. This trial completed accrual between September 2011 and November 2012. Based on the data reported in the EMILIA trial, in September 2012, the trial was Selleck Luminespib amended to allow crossover to T-DM1 in patients who had disease progression in treatment of physician��s choice. The trial randomized 602 patients, 198 to the physician treatment choice of whom 44 patients crossed over to treatment with T-DM1 at the data cutoff. The patient characteristics were even between the arms, including number of previous regimens for advanced disease, hormone receptor status, and visceral disease Volasertib clinical trial involvement. There was a slightly higher proportion of patients with previously treated symptomatic brain metastasis in the physician��s treatment choice arm (14% vs 10%). Most patients in the control arm (83%) were treated with HER2-directed agents in combination, the most common being trastuzumab and chemotherapy (68%) and lapatinib with trastuzumab (10%). PFS was increased with T-DM1, 6.2 months versus 3.3 months (HR 0.528, PSERCA the physician��s choice group, as prespecified. This benefit was also independent of hormone receptor status, number of previous treatments, the status of visceral metastasis, and the presence of previously treated brain metastasis. The final OS analysis was recently reported in San Antonio and showed a significantly longer survival with T-DM1 (median 22.7 months) compared with the control arm (median 15.8 months, P=0.0007).37 The toxicity profile was quite similar to the reports of the EMILIA trial, the most common adverse events being asthenia and thrombocytopenia (15%), though grade 3 and 4 thrombocytopenia was 5%. Globally, severe adverse events were more frequent in the physician��s treatment choice arm. Cardiac toxicity was similar between the arms, probably due to a high proportion of patients receiving trastuzumab in the control arm. However, three patients died due to the study drug from pneumonitis, hepatic encephalopathy, and subarachnoid hemorrhage. The latter was secondary to grade 4 thrombocytopenia in a patient receiving anticoagulant therapy. Oncologists should be cautious when prescribing T-DM1 with anticoagulants based on this potential interaction.