Quick Poll results from the of OncoFacts 2010
The ENESTnd phase III trial recently demonstrated that, in the front-line therapy of patients with newly diagnosed chronic phase (CP) chronic myelogenous leukemia (CML), nilotinib produced higher rates of both cytogenic complete response (CCyR) and major molecular response (MMR) and reached those therapeutic goals more quickly than did imatinib. The results of a second phase III trial comparing dasatinib versus imatinib is expected at the American Society of Clinical Oncology (ASCO) 2010 Annual Meeting. If both of these second generation tyrosine kinase inhibitors (TKIs) are approved in the front-line management of newly diagnosed CML, how will you plan to use them?
| I will continue to use imatinib front-line for almost all of my patients with newly diagnosed CML. |
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| I will only use the second generation TKIs for patients with newly diagnosed CML who are in the aggressive phase of CML. |
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| I will use a second generation TKI only for patients with newly diagnosed CP-CML at high Sokal Risk. |
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| I will use second generation TKIs for my patients with newly diagnosed CP-CML at both intermediate and high Sokal Risk. |
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| I will use second generation TKIs for almost all of my patients with newly diagnosed CP-CML. |
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Discussion
At the 2009 meeting of the American Society of Hematology, Jorge Cortes from the M. D. Anderson Cancer Center updated the results of 2 phase II studies in patients with newly diagnosed chronic phase chronic myelogenous leukemia (CP-CML) using second generation tyrosine kinase inhibitors (TKIs) in front-line therapy. Both of these trials involved approximately 60 patients with chronic phase CML and were compared with previous patient groups that had been treated with imatinib 400 mg or 800 mg daily. Complete cytogenetic response (CCYR) was achieved more rapidly with nilotinib and dasatinib compared to similar imatinib treated patients from previous trials. At 12 and 18 months, the percentage of patients in CCyR was higher for nilotinib and dasatinib compared to imatinib 400 mg but approximately the same as with imatinib 800 mg daily
CCyR rate (months) Imatinib 400 mg Imatinib 800 mg Nilotinib 800 mg Dasatinib 100 mg 3 months 37% 63% 90% 82% 6 months 54% 85% 94% 94% 12 months 65% 89% 95% 98% 18 months 67% 89% 93% 89% 24 months 67% 88% 93% 84% 36 months 67% 89% 92% 83%
Major molecular response rates at 12 months were 74% for dasatinib, 71% for nilotinib, 34% for Imatinib 400 mg, and 58% for imatinib 800 mg.
Dr Cortes and his co-investigators concluded that nilotinib and dasatinib induced more rapid CCyRs than imatinib in most patients and that adverse event profiles were acceptable and expected. In addition, cytogenetic and molecular responses at 12 and 18 months were also higher with dasatinib and nilotinib.
In addition, at the 2009 ASH Annual Meeting, Dr Giuseppe Saglio from Italy presented the initial results of the multinational ENESTnd trial in a late-breaking abstract. This was a randomized phase III trial involving 846 newly diagnosed, previously untreated patients with Philadelphia-positive (Ph1+) CP-CML. Patients were randomized to nilotinib 300 mg BID versus nilotinib 400 mg BID versus imatinib 400 mg daily. The primary endpoint was major molecular response. All patients had a minimum of 12 months treatment, and median follow-up was 14 months.
Here are the results as reported by Dr Saglio at the ASH Annual Meeting:
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Nilotinib 600 mg |
Nilotinib 800 mg |
Imatinib 400 mg |
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MMR at 6 months |
33% |
30% |
12% |
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MMR at 12 months |
44% |
43% |
22% |
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Overall MMR |
57% |
54% |
30% |
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BCR-ABL <0.01% at any time |
24% |
21% |
10% |
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CCyR at 6 months |
67% |
63% |
45% |
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CCyR at 12 months |
80% |
78% |
65% |
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PD to AP/BC at 12 months |
<1% |
<1% |
4% |
MMR, major molecular response; CCyR, complete cytogenic response; PD, disease progression; AP, accelerated phase; BC, blast crisis
Myelosuppression was greater in the imatinib arm than in the nilotinib arms. The authors concluded that “The superior efficacy and favorable tolerability of nilotinib compared with imatinib suggests that nilotinib may become the standard of care in newly diagnosed CML.”
A similar large phase III study of imatinib versus dasatinib is expected to be presented at the American Society of Clinical Oncology (ASCO) 2010 meeting. Should this trial also prove positive, as expected, physicians may soon have 1 first-generation TKI, imatinib, and 2 second-generation TKIs, nilotinib and dasatinib, from which to choose first-line therapy for patients with newly diagnosed chronic phase chronic myeloid leukemia.
References
Cortes J, Borthakur G, O’Brien S, et al. Efficacy of dasatinib in patients (pts) with previously untreated chronic myelogenous leukemia (CML) in early chronic phase (CML-CP). Blood. 2009;114(22). Abstract 338 and oral presentation at: American Society of Hematology Annual Meeting; December 5-8, 2009; San Francisco, CA.
Cortes J, O’Brien S, Jones D, et al. Efficacy of nilotinib in patients (Pts) with newly diagnosed, previously untreated Philadelphia chromosome (Ph)–positive chronic myelogenous leukemia in early chronic phase (CML-CP). Blood. 2009;114(22). Abstract 341 and oral presentation at: American Society of Hematology Annual Meeting; December 5-8, 2009; San Francisco, CA.
Saglio G, K DW, Issaragrisil S, et al. Nilotinib demonstrates superior efficacy compared with imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase: Results from the international randomized phase III ENESTnd trial. Blood. 2009;114(22). Abstract 1 and oral presentation at: American Society of Hematology Annual Meeting; December 5-8, 2009; San Francisco, CA.
* The aggregate results from this question were compiled from the responses submitted by oncologists who participated in the OncoFacts Quick Poll monthly question.