Tasigna and Sprycel Outshine Gleevec

Oncologists have begun trading in what had become a miracle pill for patients with chronic myeloid leukemia for more potent, newer-generation drugs that appear to work even better as first-line treatment for CML.

That doesn’t mean, though, that if you currently take Gleevec (imatinib) you should switch drugs, say oncologists interviewed for this article. However, the new drugs may replace Gleevec in newly diagnosed patients.

Giving Tasigna (nilotinib) or Sprycel (dasatinib) to previously untreated CML patients resulted in faster, better responses compared with Gleevec, according to research presented at the American Society of Clinical Oncology annual meeting in early June and published that same month in The New England Journal of Medicine. Two weeks after the meeting, the Food and Drug Administration approved Tasigna as a first-line treatment for CML. The agency will decide by October whether to approve Sprycel as an upfront option.

“I think that either [Sprycel] or [Tasigna] are better drugs than [Gleevec]. But you’re going from a great drug to a greater drug, so the margin of benefit is fairly small,” says Jerald Radich, MD, a leukemia specialist at Fred Hutchinson Cancer Research Center in Seattle. Tasigna and Sprycel are already approved to treat CML patients whose cancer progressed or who could not tolerate Gleevec.

For 10 years, Gleevec has been the closest thing to a cure for CML. Touted as a breakthrough, the drug has lived up to the hype. Deaths from CML dropped from 10 to 20 percent a year to 1 percent, says Hagop Kantarjian, MD, chair of the department of leukemia at M.D. Anderson Cancer Center in Houston.

In the Tasigna study, 80 percent of 282 newly diagnosed patients on Tasigna saw cancer cells completely disappear from the bone marrow after one year of therapy compared with 65 percent of 283 patients on Gleevec. Achieving this response, called a complete cytogenetic response, within a year of starting treatment is associated with better long-term survival. Tasigna beat Gleevec—in fact, had double the effectiveness of Gleevec—in eradicating the expression of the fusion gene called bcr-abl, which results from the translocation of chromosomes 9 and 22 and that defines and drives CML. For the Tasigna group, 44 percent achieved this so-called major molecular response compared with 22 percent in the Gleevec group. For newly diagnosed patients in the Sprycel study, 77 percent of 259 patients on Sprycel achieved a complete cytogenetic response compared with 66 percent of 260 patients on Gleevec after one year. The rate of major molecular response was also tipped in Sprycel’s favor: 46 percent versus 28 percent.

It’s almost an embarrassment of riches to be having conversations about how whether one drug is more wonderful than the last.

Considering the generally slow progression of CML, it will take another three to five years to see each drug’s effect on survival, says Kantarjian, who served as lead investigator on the Sprycel study and co-investigator on the Tasigna study. With Gleevec, almost 90 percent of patients are alive after 10 years.

Kantarjian says M.D. Anderson now recommends the new-generation drugs over Gleevec as first-line therapy for all patients. Radich, on the other hand, says he would start patients with low-risk disease on Gleevec and then monitor closely. He reserves Tasigna for patients with high-risk, chronic-phase CML because of the high risk for progression. For patients who are already on Gleevec and responding well to the drug, Kantarjian and Radich agree those patients should not be switched to the newer drugs.

Side effects may also narrow the choices for patients with certain health conditions. The newer agents resulted in fewer cases of nausea and fluid retention compared with Gleevec. But Tasigna can put patients at risk for an abnormal heart rhythm disorder, and Sprycel can cause fluid buildup around the lungs.

Although Kantarjian and Radich both expect the newer drugs to surpass Gleevec as first-line therapy, don’t retire the decade-old drug just yet. Generic copies of Gleevec will enter the market after the drug loses patent protection in 2015. The current wholesale price of Gleevec is about $4,200 per month, but Kantarjian estimates the generics could be as low as $410 to $830 a month. Compare that to $7,400 for a month’s supply of Tasigna and $6,950 per month for Sprycel.

Radich says research will be needed to determine the most cost-effective approach, including possibly starting patients on one of the stronger drugs and then switching to generic Gleevec for the long-term. But whether doctors and patients choose the new or the old, Radich says, “It’s almost an embarrassment of riches to be having conversations about how whether one drug is more wonderful than the last.”

Correction: The article should have stated that for newly diagnosed patients in the Sprycel study, 77 percent of 259 patients on Sprycel achieved a confirmed complete cytogenetic response compared with 66 percent of 260 patients on Gleevec after one year. We failed to note that results were confirmed twice. Initial results were 83 percent and 69 percent, respectively.