that 48 percent of patients on the new medicine appeared to have their tumors shrink, compared with 41 percent on the standard treatments. Upon further follow-up, scientists said that 64 percent on the new drug had their tumors shrink, compared with 58 percent in the control group.
One of the secondary goals of the study is to see whether patients live longer on the new treatment or not. There isn’t enough data yet from the trial to answer that question—which is the gold standard measurement of success in cancer drug development. Genentech said that so far, the number of deaths in each treatment group has been identical, and that investigators don’t consider any of the deaths to be drug-related.
Those who have been following this story closely will remember that Genentech was turned down by the FDA one year ago when it sought accelerated approval to start selling T-DM1. That application was based on a much thinner body of evidence, primarily a study that measured tumor shrinkage rates—an often important, but sometimes unreliable indicator of success—in 110 patients. Patients in that study were very sick, they were only getting the new medicine, and there was no group getting another viable therapy or placebo for comparison.
When the FDA asked for more data in August 2010, it put more of the focus on the trial being reported on today, known as 4450, and a pivotal trial of more than 1,000 patients with a similar design, called Marianne. Another study, called Emilia, is enrolling as many as 980 patients to answer a slightly different question. Those patients will be getting their second round of therapy, and they will be randomly assigned to get either the new souped-up antibody or a combination of GlaxoSmithKline’s lapatinib (Tykerb) and capecitabine (Xeloda) chemotherapy.
The Emilia trial, which could be the basis of another application to the FDA, could generate results in 2012, Pellegrino says.
