Abstract

Abstract 4443

Background:

Nilotinib and dasatinib are two therapies approved by the US Food and Drug Administration for pts with Philadelphia chromosome positive chronic myelogenous leukemia in chronic phase (Ph+ CML-CP) who are resistant or intolerant to 1st-line imatinib. Although these therapies were shown to be generally effective and tolerable, sometimes they are not, requiring treatment changes (e.g., discontinuation, dose modification, and drug holidays). To date, no head-to-head study has been conducted to compare treatment changes between 2nd-line nilotinib and dasatinibin clinical practice.

Methods:

Through an online chart abstraction form, participating community physicians retrospectively submitted de-identified information on Ph+ CML-CP pts ≥ 18 years old who switched after 10/28/2007 from imatinib to 2nd-line nilotinib or dasatinibwith at least 30 days of follow-up. When multiple pts met the selection criteria, pts were selected randomly by physicians. Pts enrolled in clinical trials or with concurrent malignancies were excluded. Information was collected on clinical characteristics and therapy changes in 2nd-line treatment, including dose modification (increase or decrease), drug holiday, and discontinuation of current therapy with or without switch to a 3rd-line therapy. Reasons for therapy changes were also collected, and treatment changes were classified as due to (1) lack of effectiveness if reasons included progression to accelerated phase or blast crisis, failure to achieve satisfactory response, or loss of satisfactory response; (2) intolerance if reasons included adverse events; (3) other reasons, including non-adherence, vacation, pregnancy, or economic reasons. Rates of treatment changes were compared between treatment groups using chi-square tests.

Results:

122 hematologists and oncologists provided information on 597 pts (301 nilotinib pts and 296 dasatinib pts). The median follow-up was 11 months (range 1–54 months) for pts on nilotinib and 10 months (range 1–56 months) for those on dasatinib. The two groups had similar age, sex, race, and comorbidities. Overall, treatment change was infrequent for both nilotinib and dasatinib patients (10% vs. 13%, p=0.40), but nilotinib pts had significantly fewer dose increases vs. dasatinib pts (0.0% vs. 1.4%, p=0.04), and they tended to have fewer drug holidays (1.7% vs. 4.4%, p=0.05). When treatment changes were classified by reason for change, nilotinib pts were less likely to change treatment due to lack of effectiveness vs. dasatinib pts (2.0% vs. 5.1%, p=0.04). Further, among pts who discontinued, fewer nilotinib pts discontinued due to lack of effectiveness (29% vs. 61%, p=0.03). Nilotinib and dasatinib pts had similar rates of treatment changes due to intolerance or other reasons, except for drug holiday, where nilotinib pts had fewer events than dasatinibpts (0% vs. 1.7%, p=0.02). The table below summarizes the changes in treatment by reason for treatment change.

Conclusions:

For Ph+ CML-CP pts on 2nd-line nilotinib or dasatinib, pts on nilotinib were less likely than those on dasatinibto change treatment due to lack of effectiveness.

NilotinibDasatinibP-value
(n=301)(n=296)
Treatment change due to lack of effectiveness, n (%) 6 (2.0) 15 (5.1) 0.04 
Discontinuation with or without switch to 3rd-line 6 (2.0) 14 (4.7) 0.06 
Dose increase 0 (0.0) 4 (1.4) 0.04 
Treatment change due to intolerance, n (%) 11 (3.7) 11 (3.7) 0.97 
Discontinuation with or without switch to 3rd-line 2 (0.7) 3 (1.0) 0.64 
Drug holiday 0 (0.0) 5 (1.7) 0.02 
Dose decrease 9 (3.0) 3 (1.0) 0.09 
Treatment change due to other reasons, n (%) 18 (6.0) 13 (4.4) 0.38 
Discontinuation with or without switch to 3rd-line 13 (4.3) 6 (2.0) 0.11 
Drug holiday 5 (1.7) 8 (2.7) 0.38 
NilotinibDasatinibP-value
(n=301)(n=296)
Treatment change due to lack of effectiveness, n (%) 6 (2.0) 15 (5.1) 0.04 
Discontinuation with or without switch to 3rd-line 6 (2.0) 14 (4.7) 0.06 
Dose increase 0 (0.0) 4 (1.4) 0.04 
Treatment change due to intolerance, n (%) 11 (3.7) 11 (3.7) 0.97 
Discontinuation with or without switch to 3rd-line 2 (0.7) 3 (1.0) 0.64 
Drug holiday 0 (0.0) 5 (1.7) 0.02 
Dose decrease 9 (3.0) 3 (1.0) 0.09 
Treatment change due to other reasons, n (%) 18 (6.0) 13 (4.4) 0.38 
Discontinuation with or without switch to 3rd-line 13 (4.3) 6 (2.0) 0.11 
Drug holiday 5 (1.7) 8 (2.7) 0.38 
Disclosures:

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. Chen:Novartis Oncology: Employment, Own stock in Novartis Other. 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. 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. Griffin:Novartis: Consultancy, Research Funding.

Author notes

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Asterisk with author names denotes non-ASH members.