June 8, 2010 (Chicago) -- Two newer drugs, Sprycel and Tasigna, beat out the groundbreaking cancer drug Gleevec in treating people with newly diagnosed chronic myeloid leukemia (CML), researchers report.
In separate studies, both newer drugs were associated with substantially better response rates compared with the older Gleevec.
Sprycel and Tasigna are currently approved to treat patients for whom Gleevec fails.
The new findings, presented at the American Society of Clinical Oncology annual meeting in Chicago and published online June 5 in the New England Journal of Medicine, suggest they should be considered as first-line treatment.
When Gleevec came on the market in 2001, it was considered revolutionary -- one of the first targeted therapies to seek out and destroy only cancer cells, leaving surrounding healthy tissue unscathed. Not only do such targeted therapies typically work better, but they help to avoid many of the side effects, such as nausea and hair loss, associated with traditional chemotherapy.
Overnight, the pill became the standard treatment for CML because it was relatively safe, easy to administer, and worked fast to produce excellent clinical remissions, says Sonali Smith, MD, of the University of Chicago Medical Center.
Studies have shown at least 80% of patients on Gleevec are still alive eight to 10 years after starting treatment. In contrast, the long-term survival rate was less than 20% in the pre-Gleevec era.
Gleevec targets a mutation in the protein BCR-ABL, which allows cells to multiply unchecked. Sprycel and Tasigna block the same pathway, but in slightly different and more potent ways, says Smith, who moderated a news briefing on the Sprycel findings.
Sprycel vs. Gleevec
The first study involved 519 patients with newly diagnosed CML randomly assigned to take either Sprycel or Gleevec.
After one year, cancer cells were almost completely wiped out in the bone marrow of 77% of patients receiving Sprycel, compared with 66% of patients receiving Gleevec.
Also, 46% of patients on Sprycel had a major molecular response, meaning that the amount of BCR-ABL in their blood was barely detectable, vs. 28% on Gleevec.
Patients on Sprycel responded more quickly, says Hagop Kantarjian, MD, an oncologist at University of Texas M.D. Anderson Cancer Center in Houston who worked on both studies.
A total of 1.9% of patients on Sprycel and 3.5% of patients on Gleevec progressed to more aggressive states of CML known as accelerated or blast phases, in which leukemia cells build up and become more abnormal, causing symptoms to appear or become more serious.
While it's too soon to know if the drug extends lives, the improved responses in the Sprycel group suggest "it will significantly improve the long-term outcome" of CML patients, Kantarjian tells WebMD. The patients continue to be followed.
Kantarjian consults for Sprycel maker Bristol-Myers Squibb, which funded this study, as well as Novartis Pharmaceuticals, which makes Tasigna and Gleevec and funded the second study.
Tasigna vs. Gleevec
In the second study of 846 patients, cancer cells were almost completely wiped out in the bone marrow of about 80% of patients on Tasigna by one year, compared with 65% of patients on Gleevec. The rates of major molecular response were about 44% and 22%, respectively.
Tasigna "produced more responses and better outcomes for patients," says study head Giuseppe Saglio, MD, of the University of Turin, Italy.
All three drugs "have outstanding safety profiles," Charles Sawyers, MD, of Memorial Sloan-Kettering Cancer Center in New York, writes in an editorial in the New England Journal of Medicine. There are modest differences in side effects that may lead one patient to choose one drug over another, he writes.
For example, muscle cramps and fluid retention are more common with Gleevec, while changes on liver function tests are more common with Tasigna, he writes. Rashes and headache were more common among both Sprycel and Tasigna users than among patients on Gleevec in the new studies.
But one-year results may make it too early to "claim complete victory" against CML, Sawyers writes.
Ironically, it may come down to economic considerations, he writes, noting that Gleevec could become available in a much cheaper generic form when its patent expires in a few years.
Currently, a month's supply of Gleevec costs about $4,200, and Tasigna can run $7,900 per month, according to Novartis, which makes both drugs.
Smith says that based on the research to date, the FDA is expected to consider approving both newer drugs for newly diagnosed patients.
Another targeted CML drug, bosutinib, made by Pfizer, is also in testing.