Abstract

Abstract 2796

Background:

Nilotinib and dasatinib are two tyrosine kinase inhibitors (TKIs) commonly used for the treatment of patients with chronic myelogenous leukemia in chronic phase (CML-CP) who are resistant or intolerant to imatinib. Both TKIs have been shown to be more potent than imatinib. However, no head-to-head clinical trials have been conducted comparing the efficacy of nilotinib to dasatinib as 2nd-line therapy for CML-CP patients resistant or intolerant to imatinib. This study compared disease outcomes of patients treated in the community who were switched from imatinib to 2nd-line nilotinib or dasatinib.

Methods:

Through an online chart abstraction form, participating community physicians submitted de-identified information on CML-CP patients ≥ 18 years old who switched after 10/28/2007 from imatinib to 2nd-line nilotinib or dasatinib with at least 30 days of follow-up. When multiple patients met the selection criteria, up to 8 patients in each group were selected randomly by physicians. Patients enrolled in clinical trials or with concurrent malignancies were excluded. Information was collected on demographics, clinical characteristics, cytogenetic response, progression to accelerated phase or blast crisis, and death from any cause. Documented complete cytogenetic response (CCyR) at a particular time point was defined as 0% Philadelphia chromosome positive cells on cytogenetic testing; patients with missing tests at that time point were counted as non-responders. Disease progression to accelerated phase or blast crisis, progression-free survival, and overall survival were compared using multivariate Cox proportional hazards models, adjusting for potential confounding factors, including patient demographics and clinical characteristics at the time the patient switched to a 2nd-line TKI.

Results:

122 hematologists and oncologists provided information on 597 patients, including 301 patients on nilotinib and 296 patients on dasatinib. The median follow-up was 11 months for nilotinib patients and 10 months for dasatinib patients. Age, sex, race, comorbidities, and other clinical characteristics were similar for both groups, except that nilotinib patients were more likely than dasatinib patients to have switched due to secondary imatinib resistance (p=0.047) and were less likely to have switched due to imatinib intolerance (p=0.024). Nilotinib patients had similar rates of documented CCyR compared to dasatinib patients at 12 months (37% vs. 35%, p=0.54), 24 months (42% vs. 40%, p=0.62), and 36 months (44% vs. 44%, p=0.95) following the switch. However, nilotinib patients had lower risk of progression (p=0.004), higher progression free survival (p=0.023) and a trend towards prolonged overall survival (p=0.067), adjusting for potential confounders. The table below summarizes these results.

Conclusions:

Among patients with CML-CP switched to nilotinib or dasatinib for 2nd-line therapy, nilotinib patients had significantly lower rates of progression and longer progression-free survival compared to dasatinib patients.

Outcome Nilotinib Events Dasatinib Events Unadjusted Hazard Ratio P-value Adjusted Hazard Ratio P-value 
(n=301) (n=296) 
Progression 5 (1.7) 13 (4.4) 0.39 (0.14–1.09) 0.072 0.15 (0.04–0.55) 0.004 
Progression-free Survival 286 (95.0) 269 (90.9) 1.81 (0.96–3.40) 0.067 2.14 (1.11–4.12) 0.023 
Overall Survival 291 (96.7) 279 (94.3) 1.71 (0.78–3.75) 0.177 2.13 (0.95–4.78) 0.067 
Outcome Nilotinib Events Dasatinib Events Unadjusted Hazard Ratio P-value Adjusted Hazard Ratio P-value 
(n=301) (n=296) 
Progression 5 (1.7) 13 (4.4) 0.39 (0.14–1.09) 0.072 0.15 (0.04–0.55) 0.004 
Progression-free Survival 286 (95.0) 269 (90.9) 1.81 (0.96–3.40) 0.067 2.14 (1.11–4.12) 0.023 
Overall Survival 291 (96.7) 279 (94.3) 1.71 (0.78–3.75) 0.177 2.13 (0.95–4.78) 0.067 
Disclosures:

Griffin:Novartis: Consultancy, Research Funding. Guerin:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Chen:Novartis Oncology: Employment, Own stock in Novartis Other. Macalalad:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Luo:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding. Wu:Analysis Group, Inc.: Consultancy, Employment, I am an employee of Analysis Group, Inc, which has received consulting fees from Novartis Pharmaceuticals Other, Research Funding.

Author notes

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Asterisk with author names denotes non-ASH members.