DTC Key Efficacy and Safety Data


Dr Andrew Gianoukakis reviews the study design and key efficacy data of the phase 3 DECISION and SELECT trials.

Andrew Gianoukakis, MD: The phase 3 DECISION trial was performed between October 2009 and July 2011. This trial was 400 mg of sorafenib orally, twice daily, versus placebo in a 1:1 randomization scheme with 417 enrolled patients. Patients who were included had locally advanced or metastatic RAI [radioactive iodine]-refractory disease. Progression over the previous 14 months was based on RECIST criteria; patients were excluded if they had received prior chemotherapy, targeted therapy, or thalidomide. The primary end point was progression-free survival, with a few secondary end points, and patients both under and over the age of 60 were included and stratified. The Kaplan-Meier survival curve, noted on the left panel, indicated the progression-free survival advantage of sorafenib versus placebo, with an overall response rate of 12.2% in the sorafenib-treated arm and 0.5% in the placebo arm. Overall survival was not reached. In terms of safety, sorafenib was associated with a significant percentage of treatment-related adverse effects, which lead to treatment-related adverse events [AEs] and dose interruptions and dose reductions, as well as withdrawals, compared to placebo. Most notably, hand-foot skin reaction was the most common reason for sorafenib dose reductions and withdrawals. Looking at the most significant grade 3 and 4 AEs, as noted, hand-foot syndrome, diarrhea, weight loss, hypertension and fatigue were all common in the sorafenib arm compared to the placebo arm and do lead to the decrease in quality of life that was mentioned earlier with these medications.

The lenvatinib SELECT trial, the phase 3 trial was global, randomized and double-blinded. In this case it was a 2:1 randomization between lenvatinib and placebo. Patients needed to exhibit disease progression in the prior 13 months, based on RECIST. The patients needed to be iodine-refractory and have measurable disease, and up to 1 prior VEGF-targeted therapy was allowed. The study also included patients less than and over 65 years of age and was also stratified based on that. The primary end point was progression-free survival, and there was an optional open-label continuation trial where patients who were initially on placebo could transition to active drug after progressing. The Kaplan-Meier curve, noted here, indicated a progression-free survival of 19.4 months versus 3.7 months for the lenvatinib versus placebo. The waterfall plots, as we can see here, indicate the very nice response seen with lenvatinib, where a combination of PR [partial response] and CR [complete response] rose to nearly 65%, versus 1.5% in the placebo arm. In terms of safety for lenvatinib, similar to sorafenib, there was a significant number of treatment-related adverse events that lead to dose reductions and discontinuations. Discontinuations of the drug due to adverse events was 14.2% in the lenvatinib group versus 2.3% in the placebo group, and there were a few severe treatment-related events, notably deaths, on the lenvatinib arm.

This transcript has been edited for clarity.

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