Imatinib, better known as Gleevec, has been one of the most successful cancer drugs ever developed. The targeted therapy has increased the five-year survival rate among those with chronic myeloid leukemia from 50% to 90%.
Second-generation drugs that block even more variations of the CML-causing protein have been approved as second-line therapy for those whose disease grows resistant to Gleevec.
Two new studies published in the New England Journal of Medicine and presented at the 46th Annual Meeting of the American Society of Clinical Oncology show that the newer drugs, nilotinib and dasatinib, provide faster, better remissions and do a better job blocking disease progression to more advanced stages when they are given to new CML patients instead of Gleevec.
"The second-generation CML drugs are more effective than imatinib and less toxic overall," says Hagop Kantarjian, M.D., professor and chair of MD Anderson's Department of Leukemia. Kantarjian is the corresponding author of the dasatinib study and co-author of the nilotinib study.
The large, Phase III clinical trials compared the drugs using two measures of high-quality remission: complete cytogenetic response and major molecular response after a year of treatment. Achieving either has been shown to extend survival. The studies also looked at disease progression. Nilotinib and dasatinib were superior to Gleevec in all areas.
"We've learned in cancer therapy that it's important to use your big guns up front," Kantarjian says. "Using these second-generation drugs first will likely improve outcomes for patients with chronic myeloid leukemia."
An accompanying editorial in the New England Journal puts the findings in perspective and touches on medical and economic reasons that might favor one of the three drugs over the others.
MD Anderson has been extensively involved in planning and operating clinical trials for all three drugs. The two new studies confirm results from single-arm clinical trials conducted at MD Anderson comparing the performance of the drugs in new patients to historical results from earlier trials of Gleevec.
MD Anderson News Release: Second-line CML Drugs Evoke Faster, Better Front-line Remissions