Dasatinib Tested First Line for Chronic Myelogenous Leukemia

Allison Gandey

June 03, 2007

June 3, 2007 (Chicago) -- The first study to explore the possibility of dasatinib ( Sprycel, Bristol-Myers Squibb) graduating to a standard of care for patients with newly diagnosed chronic myelogenous leukemia is showing promise, with strong drug activity and rapid cytogenetic response. The phase 2 trial of dasatinib was presented here at the 43rd Annual Meeting of the American Society of Clinical Oncology. "This is an interesting study, and it looks like there is a benefit of using dasatinib first line with very rapid responses," Dean Bajorin, MD, from Memorial Sloan-Kettering Cancer Center, in New York, and moderator of a press conference outlining the findings, told Medscape.

The current standard of care is imatinib ( Gleevec, Novartis). Both products are multitargeted kinase inhibitors of BCR-ABL and SRC. An estimated 1% to 2% of patients cannot tolerate imatinib, and many others go on to develop drug resistance. Dasatinib is currently approved as a second-line treatment for patients requiring an alternative to imatinib. "Drug resistance is really a partial response," Dr. Bajorin said. "Wouldn't it be great if, instead of developing resistance, patients on dasatinib experienced a complete response? It appears from this study that dasatinib is much more biologically active, and I think we are going to hear more about this in the future."

During an interview with Medscape, lead investigator Ehab Atallah, MD, from the University of Texas MD Anderson Cancer Center, in Houston, agreed the drug is beneficial, with responses occurring as early as at 3 months, but he admitted that resistance will also be a problem with this kinase inhibitor. "Some patients will be resistant," he said. But Dr. Atallah hopes that the seemingly faster responses to therapy will pay off. "This is a debatable issue, but this is what we are anticipating. Our hypothesis is that patients who have a better early hematologic response may have better progression-free and overall survival."

Responses Occurred as Early as 3 Months

During the discussion period following the presentation, Charles Schiffer, MD, from the Karmanos Cancer Institute at Wayne State University School of Medicine, in Detroit, Michigan, questioned the importance of a rapid response. "This could be like the tortoise and the hare. . . . Does it really matter who reaches the finish line first, as long as we achieve a complete cytogenetic response?"

Session chair Ellin Berman, MD, from the Memorial Sloan-Kettering Cancer Center also raised questions about the number of dose interruptions in the study. She was concerned that the rate, at 43%, was high. "This strikes me as difficult from a management perspective compared with imatinib," she said.

During an interview with Medscape, Dr. Atallah said dose interruptions for dasatinib do tend to be a bit higher than imatinib and the toxicities also tend to be greater. "These are low-grade toxicities," he said, "but they are a bit higher." The main adverse events for dasatinib are generally pain, fatigue, skin rash, and headache.

The study looked at just over 30 chronic myelogenous leukemia patients with no prior therapy or less than 1 month of previous treatment. Patients were randomized to receive oral dasatinib at doses of either 50 mg twice daily or 100 mg once a day. There were no differences found between the 2 doses.

Overall Response on Dasatinib (n=34)

n (%)
Complete cytogenetic response
29 (85)
Partial cytogenetic response 2 (6)
Minor cytogenetic response
1 (3)
Early or insufficient metaphases
2 (6)

Major Cytogenetic Responses
3 mo (n=31), %
6 mo (n=26), %
12 mo (n=21), %
Complete cytogenetic response
Partial cytogenetic response

To put these preliminary results into perspective, the researchers compared these findings with other recent MD Anderson studies. In those analyzes, 54% of patients receiving the lower standard dose of imatinib of 400 mg and 85% of patients receiving a higher dose of imatinib of 800 mg had a complete cytogenetic response after 6 months of therapy.

Discussing the limitations of the present trial, Dr. Atallah pointed to the limited number of patients in the study and the short follow-up. He noted that his team will continue to follow patients, and several large multi-institutional phase 3 trials are now enrolling and are under way to compare first-line dasatinib and imatinib head to head.

American Society of Clinical Oncology 43rd Annual Meeting: Abstract 7005. Presented June 2, 2007.


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