Novartis presents new data from large European study reinforcing the benefit of first-line Tasigna® in newly-diagnosed patients with CML - Seite 2

"Our commitment to CML remains strong and is exemplified by this trial, as well as further study of deep molecular response with Tasigna and the possibility for some patients with Ph+ CML to stop their treatment and achieve sustained treatment-free remission," said Bruno Strigini, President, Novartis Oncology. "In addition, we are developing new compounds with different mechanisms of action, which could help address the resistance to existing medications that some patients experience."

ENEST1st Study Details[1]
ENEST1st (Evaluating Nilotinib Efficacy and Safety Trial as First-Line Treatment) is a Phase 3b, open-label study that evaluated the efficacy and safety of Tasigna 300 mg twice daily (BID) in a large population of adult patients with newly diagnosed CML-chronic phase (CP) using a network of 14 European Treatment and Outcome Study (EUTOS) standardized laboratories to monitor MR. 

The study was conducted in 26 European countries with 1,089 patients treated. Specifically, 90.3% of patients were Philadelphia chromosome positive (Ph+) and 97.0% had typical BCR-ABL transcripts. Sokal risk scores were low, intermediate and high in 34.6%, 37.5% and 18.1% of patients, respectively (9.8% missing). EUTOS scores were low in 82.6% and high in 8.6% of patients (8.7% missing). A total of 80.9% of patients completed 24 months of treatment; 19.1% discontinued early, most frequently due to AEs (10.7%). The AEs seen in this study were consistent with the known safety profile of Tasigna. Thirteen patients (1.2%) died by 24 months; of those 13 deaths, one was attributed to CML progression (16 months after study drug discontinuation).

The primary endpoint was the rate of MR4.0 (BCR-ABL <=0.01% on the International Scale [BCR-ABL^IS] or undetectable BCR-ABL in cDNA with >=10,000 ABL transcripts) at 18 months. The MR4.0 rate in all treated patients with <=3 months of prior Glivec treatment (n=1,052) was 38.4% at 18 months and 40.4% at 24 months. As assessed with multicenter molecular monitoring, MR rates in this study provided prospective confirmation of the centrally reviewed MR rates in the pivotal ENESTnd study. In ENESTnd, Tasigna demonstrated higher rates of early and deeper sustained molecular response, including MR4.5, and a reduced risk of progression compared to Glivec.

Consistent with prior studies, ENEST1st demonstrated the importance of early molecular response to frontline treatment. Molecular testing can vary in countries around the world, thus reinforcing the importance of these consistent findings. Patients with BCR-ABL1^IS <= 1% at 3 months achieved the highest rates of MMR, MR4.0, and MR4.5 at later time points, while no patient with BCR-ABL1^IS > 10% at 3 months achieved MR4.0 by 24 months.

Within the study duration of two years, the most common AEs of any cause were rash (21.4%), itch (16.5%), and headache (15.2%). Study investigators conclude relatively low rates of these AEs may reflect improvements in the management of Tasigna-treated patients. Peripheral artery disease (PAD) occurred in 1.9% of patients, ischemic heart disease (IHD) in 3.4%, and ischemic cerebrovascular conditions (ICVE) in 0.8%; 0.6% of patients had excess fluid around the lung. These findings are consistent with what was seen in ENESTnd at the same duration of therapy. The most frequently observed grade 3/4 biochemical abnormalities were decreased phosphate (14.3%) and increased lipase (7.2%); glucose and lipid monitoring was not mandated in the study protocol.