New data from a large, international clinical trial find that patients with newly diagnosed chronic myeloid leukaemia who received Glivec (imatinib) at 800 mg/day as their initial treatment achieved clinical milestones significantly faster than those receiving the standard 400 mg/day dose.

The Tyrosine Kinase Inhibitor Optimization and Selectivity Study (TOPS) is the first phase III, randomized, controlled clinical trial designed to evaluate the potential benefits of an 800 mg starting dose across all risk categories of newly diagnosed, previously untreated patients with Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML).

Numerically, more patients achieved a major molecular response (MMR) with the 800 mg dose than the 400 mg dose (46.4% vs. 40.1%); however, the difference between the two arms -- the primary endpoint of the study -- was not statistically significant. This trend of improved MMR rate at 12 months in the 800 mg vs. 400 mg arms was most pronounced in the subset of patients with the highest risk for disease progression (41.1% vs. 26.2%). Further, patients in the 800 mg arm achieved MMR significantly faster than those who started treatment with Glivec at 400 mg. Achievement of a MMR is an important goal of therapy for CML.

"TOPS reaffirms Glivec as the standard of care for newly diagnosed CML patients," said Jorge Cortes, MD, Professor of Medicine and Deputy Chair of Leukaemia at the University of Texas MD Anderson Cancer Center in Houston. "We see a strong trend for rapid response with the 800 mg dose. As with trials like IRIS, further follow up will be needed to assess what this rapid early response will mean in terms of long-term benefit."

TOPS also showed that patients with lower blood levels of Glivec at one month had a lower molecular response at a year, an observation made in previous studies. Cumulatively, these data suggest that maintaining adequate blood levels may help attain better clinical responses.

These findings, from the first analysis of the TOPS data set, will be presented on Saturday, June 14, at the 2008 Congress of the European Hematology Association (EHA) in Copenhagen.

"Our robust clinical program with Glivec continues to provide meaningful insights into the treatment of Ph+ CML and other types of cancer," said Diane Young, MD, Head of Global Medical Affairs at Novartis Oncology. "Novartis continues to invest in trials like ENESTnd, which is comparing Tasigna to Glivec in the first-line setting, to build on this knowledge and further enhance treatment outcomes for patients."
ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials of newly diagnosed Ph+ CML patients) is designed to study the efficacy and safety of Tasigna (nilotinib) vs. Glivec in newly diagnosed patients in the chronic phase. ENESTnd is currently underway and will enroll approximately 771 patients at 220 centers worldwide. Tasigna is currently approved for the treatment of Ph+ CML in the chronic or accelerated phase in patients resistant to, or intolerant of, Glivec.

Glivec is approved in more than 90 countries, including the US, EU and Japan, for the treatment of all phases of Ph+ CML. Glivec is also approved in the EU, US and other countries for the treatment of patients with Kit (CD117)-positive gastrointestinal tumors (GIST), which cannot be surgically removed and/or have already spread to other parts of the body (metastasized). In Japan, Glivec is approved for the treatment of patients with Kit (CD117)-positive GIST. In the EU, Glivec is also approved for the treatment of adult patients with newly diagnosed Ph+ acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy and as a single agent for patients with relapsed or refractory Ph+ ALL. Glivec is also approved for the treatment of adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP) who are not eligible for surgery. Glivec is also approved for the treatment of patients with myelodysplastic / myeloproliferative diseases (MDS/MPD). Glivec is also approved for hypereosinophilic syndrome and/or chronic eosinophilic leukemia (HES/CEL).