everolimus drug fails to improve overall survival in patients with advanced liver cancer -
Despite strong preclinical data, drug everolimus has failed to improve overall survival in patients with advanced liver cancer, compared with placebo, according to a study published in the July 2 issue of JAMA
patients with advanced hepatocellular carcinoma. (HCC, a type of liver cancer) have a median overall survival of less than one year, largely because of the lack of effective treatments. The drug sorafenib is the only systemic therapy shown to significantly improve overall survival in advanced HCC; but its benefits are often transitory and modest, and the disease eventually progresses. In preclinical models, everolimus prevented tumor progression and improved survival, according to background information in the article.
Andrew X. Zhu, MD, Ph.D., of the Hospital Cancer Center at Massachusetts General, Harvard Medical School, Boston, and colleagues randomly assigned 546 adults with advanced HCC whose disease progression during or following sorafenib or sorafenib were intolerant to receive everolimus (n = 362) or placebo (n = 184), both given in combination with best supportive care and continued until progression of the disease or intolerable toxicity. In this phase 3 study, patients were recruited from 17 countries between May 2010 and March 2012.
The researchers found no significant difference in overall survival between the two groups, there were 303 deaths ( 83.7 percent) in the everolimus group and 151 deaths (82.1 percent) in the placebo group. The median overall survival was 7.6 months with everolimus, 7.3 months with placebo. disease control rate (percentage of patients with a better overall response of the complete or partial response or stable disease) was 56.1 percent (everolimus) and 45.1 percent (placebo).
"The results of [this study, EVOLVE-1] extend the list of failed phase 3 study in advanced HCC, highlighting the challenge of developing effective therapies for this cancer," the authors write.
the researchers note that the EVOLVE-and the other phase 3 studies failed provided several important lessons, including that it is difficult to assess the effectiveness of Phase 2 testing signals; endpoints substitution such as time to progression, progression free survival and response rate incompatible predict overall survival in Phase 3 trials, and clinical and biological heterogeneity likely affects the performance of targeted therapies in HCC "in the. lack of predictive biomarkers well characterized and validated, the targeted agents are likely to continue to have a high risk of failure if the phase 3 trials are performed in non-selected populations. "
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