2项III期临床试验进一步证实了诺华新型抗癌药物Tasigna（尼洛替尼）相较于格列卫（Glivec,伊马替尼）在费城染色体阳性慢性髓细胞白血病（Ph+CML）患者中的临床治疗益处。
ENESTcmr临床试验表明，接受格列卫长期治疗但仍残留病灶的患者，转向Tasigna治疗后，取得了更深层次的分子反应。Tasigna治疗组中，取得不可检测水平BCR-ABL的患者数目是格列卫治疗组的2倍多。
ENESTnd临床试验表明，将格列卫与Tasigna作为一线治疗药物时，Tasigna治疗组在3个月和6个月时实现早期分子反应（BCR-ABL水平降至≤10%）的患者数是格列卫的3倍多，预示着疾病无进展生存期及总生存期有可能增加.
临床试验详细数据：
ENESTcmr study details
ENESTcmr (Evaluating Nilotinib Efficacy and Safety in Clinical Trials - Complete Molecular Response) is an open-label, randomized, prospective, multi-center Phase III study of Tasigna 400 mg twice daily versus standard-dose Glivec (400 mg or 600 mg once daily) comparing kinetics of molecular response for patients with Ph+ CML in chronic phase who had achieved complete cytogenetic response (CCyR) but were still BCR-ABL positive (i.e., had evidence of residual leukemia) after at least two years of treatment with Glivec. The study enrolled 207 patients. The patients were randomized into one of two treatment arms: Tasigna 400 mg twice daily versus continuing Glivec 400 mg or 600 mg once daily (same dose as at study entry).
The primary endpoint was the rate of confirmed best complete molecular response by 12 months of study therapy with Tasigna or Glivec. Secondary objectives included the kinetics of molecular response, duration of molecular response, progression-free survival and overall survival in both arms. These data, presented at ASH, were the 24-month follow-up.
More than twice as many patients treated with Tasigna continued to achieve undetectable BCR-ABL versus Glivec. The difference between groups by 24 months was statistically significant (22.1% vs. 8.7%; p=0.0087). Compared to the 12-month analysis, the difference between the treatment arms doubled over time from 6.7% to 13.4%. Among patients without documented MR4.5 at baseline, cumulative incidence of MR4.5 was over twice as high in Tasigna-treated patients versus those who stayed on Glivec (42.9% vs. 20.8%; p=0.0006) and the difference increased over time from 12 to 24 months. Significantly more patients treated with Tasigna achieved MR4.5 versus Glivec regardless of the BCR-ABL transcript level at baseline. In patients without documented MMR, MR4 and MR4.5 at baseline, the differences were superior in all subsets (29.2% vs. 3.6%; p=0.016; 31.1% vs. 11.5%; p=0.003 and 42.9% vs. 20.8%; p=0.0006, respectively).
ENESTnd study details
ENESTnd (Evaluating Nilotinib Efficacy and Safety in Clinical Trials - Newly Diagnosed Patients) is a Phase III randomized, open-label, multicenter trial comparing the efficacy and safety of Tasigna versus Glivec in adult patients with newly diagnosed Ph+ CML in chronic phase. It is the largest global randomized comparison of two oral therapies ever conducted in newly diagnosed Ph+ CML patients,,.
The study is being conducted at 217 global sites with 846 patients enrolled. Patients were randomized to receive Tasigna 300 mg twice daily (n=282), Tasigna 400 mg twice daily (n=281) or Glivec 400 mg once daily (n=283). The primary endpoint was major molecular response (MMR) at 12 months; the key secondary endpoint was durable MMR at 24 months (patients having MMR when evaluated at both 12 and 24 months). MMR was defined in this study as 0.1% or less of BCR-ABL as measured by RQ-PCR. Planned follow-up is for five years. Patients on the Glivec treatment arm who had suboptimal response or treatment failure were allowed to escalate dose and/or switch to Tasigna in a separate extension study. These data, presented at ASH, were the 48-month minimum follow-up,,.
The ENESTnd landmark analysis was based on BCR-ABL transcript levels at three and six months using data with a minimum follow-up of four years. The Tasigna 300 mg BID (n=282) and Glivec 400 mg QD (n=283) treatment arms were used for the analysis. Rates of MMR, MR4.5, progression-free survival and overall survival were evaluated among patients grouped according to their BCR-ABL transcript levels of <=1%, >1% to <=10%, and >10% at three and six months. Among evaluable patients at three months, 9% of patients (n=24) in the Tasigna arm versus 33% (n=88) in the Glivec arm had BCR-ABL transcript levels of >10%. Patients with a BCR-ABL transcript level of >10% had a significantly lower probability of future MMR or MR4.5as well as poorer progression-free survival and overall survival compared with patients who had BCR-ABL transcript levels <=10% at three months. Fewer patients in the Tasigna arm versus the Glivec arm had BCR-ABL transcript levels >10% at three and six months. Early molecular response at three and six months correlated with future MMR and MR4.5as well as an increased probability of progression-free survival and overall survival.
The four-year ENESTnd update found continued significantly higher rates of MMR, MR4 and MR4.5by three years were achieved in Tasigna versus Glivec-treated patients. The difference in the rates of both MR4 and MR4.5continued to be significantly higher for Tasigna, with the difference in favor of Tasigna increasing from year one to year four (MR4: 9-14% difference by one year, 17-24% difference by four years; MR4.5: 6-10% difference by one year, 14-17% difference by four years). Among patients who achieved MMR, more patients achieved MR4 or MR4.5on Tasigna 300 mg twice daily (68%) and Tasigna 400 mg twice daily (62%) compared with Glivec (49%). No patient in any arm progressed after achieving MR4.5. Significantly fewer patients progressed to accelerated phase/blast crisis on Tasigna versus Glivec. Nearly twice as many patients had emergent mutations on Glivec (n=21) versus either Tasigna arm (n=11 in each arm), with five patients overall developing mutations between two and three years. Overall survival remained similar in all groups at three years, but fewer CML-related deaths occurred in both the Tasigna 300 mg twice daily (n=5) and 400 mg twice daily (n=4) arms versus Glivec (n=14). Both drugs were well tolerated. Few new adverse events (AEs) and laboratory abnormalities were observed between two and three years. Rates of discontinuation due to AEs were 10%, 14%, and 11% in the Tasigna 300 mg BID, Tasigna 400 mg BID, and Glivec arms, respectively.
