Skip Navigation U.S. Department of Health and Human Services www.hhs.gov
Agency for Healthcare Research Quality www.ahrq.gov
Archive print banner
Report on the Relative Efficacy of Oral Cancer Therapy for Medicare Beneficiaries Versus Currently Covered Therapy

This information is for reference purposes only. It was current when produced and may now be outdated. Archive material is no longer maintained, and some links may not work. Persons with disabilities having difficulty accessing this information should contact us at: https://info.ahrq.gov. Let us know the nature of the problem, the Web address of what you want, and your contact information.

Please go to www.ahrq.gov for current information.

Table 3. Summary of Efficacy of Imatinib for CML—Chronic Phase, Interferon Resistant or Refractory

  Study ID Imatinib dose [median length of followup] No. of patients, age, sex, additional CML characteristics N Major
CR
Complete
CR
Partial
CR
Minor
CR
Minimal
CR
CHR Survival/
Other
Phase I/II Druker, Talpaz, et al., 200166 25-1000 mg/d [8.5 mo (1 wk to 8.5 yr)] 83 pts
55 [19-76]
66% M
I = 83           77% Median time to best cytogenetic response = 147 days
I Dose:            
<50 mg= 6           0%
85 = 4           25%
140 =3           33%
200-250=16           56%
300-1000=54           99%
Higher dose ranging:            
330-350mg 38%     15%    
400 50%     33%    
500 17%     17%    
600 50%     50%    
750 33%     0%    
800 12%     25%    
1000 14%     1%    
Total N = 54 31%     22%    
Braziel, 2002 sub-study67 300-600 mg

[mean 3.5 yr; range 1.1-9.1 yr.]
19 pts

57[19-70]
47% M
I = 19 64% 32% 32%     95% All pts with CCR were still cytogenetically negative at 14 mo; 5/6 also with CMR
Kantarjian, Sawyers, et al., 20022 400 mg

(increased to 800 mg for no CHR at 3 months, no MCR at 12 months, or relapse after CHR)

[med duration of treatment with I = 17.9 mo (0.5-20.3)]
532 pts
57 yrs. [18-81]
60% M

454 of these were confirmed chronic phase patients
I = 454 60% 41% 19% 5% 11% 95% Median 18 mo PFS = 89% (95% CI, 86 to 92%)
IFN/ hematologic failure: Resistance = 63 41% 25% 16% 8% 16% 89% Median 18 mo OS = 95%
Relapse = 70 57% 41% 16% 1% 16% 99% Median time to cytogenetic relapse 12 mo (range 6-19) and 6 mo (range 3-14) from time of MCR
IFN/
cytogenetic failure:
Resistance = 119
55% 31% 24% 8% 9% 97% If dose increase necessary, CHR in 9% and CR in 11%
Relapse= 41 83% 76% 7% 2% 2% 98%  
IFN intolerant = 161 66% 47% 19% 2% 11% 93%  
Marin, Marktel, Szydlo, et al., 2003 sub-study68   Subset of 143 pts
>60yr = 24%
54%M
I = 143 55% 34% 19% 4%     Treatment with I:
RR for mortality 0.54 (CI 0.31-0.93, p=0.026)
Historical controls = 246 CML CP pts from the Medical Research Council CML 3 trial of IFN vs busulfan or hydroxyurea who didn't respond to IFN Historical control = 246             RR for PFS 0.40 (CI 0.20-0.77, p=0.0065)
Cortes, Giles, et al, 200369 800 mg
[15 mo]
33 pts
47 [30-75]
22% >60 yr
42% M
I = 33 90%

97% durable
89%         All alive at 16 mo median f/u, except two that stopped therapy (1 = arthritis; 1= noncompliant)
Karntarjian, Talpaz, et al., 200270

Includes some patients presented in Kantarjian, Sawyers, et al., 20022
400 mg

(increased to 800mg for no CHR at 3 months, no MCR at 12 months, or relapse after CHR)

[17 mo (1-21)]
249 pts
34% >60 yrs
57%M
I = 249 62% 45%         18 mo PFS = 93%
3 mo 44% 25%         18 mo OS = 96%
6 mo 47% 28%         Any cytogenetic response at 3 months:
Yes—PFS at 18 mo = 100%
No—PFS at 18 mo = 85%
   (p<0.001)
12 mo 57% 38%         Yes—OS at 18 mo = 100%
No—OS at 18 mo = 95%
   (p<0.001)
Karntarjian, Talpaz, et al., 200371

Includes patients from Kantarjian, Sawyers, et al., 20022 and Karntarjian, Talpaz, et al., 200270
400-800 mg

Planned dose escalation from 400 mg to 800 mg, or to 600 mg daily if the dose had been reduced to 300 mg daily if no CHR at 3 mo, no MCR at 12 mo, heme relapse, or cytogenetic relapse, defined as an increase of Ph+ cells by at least 30%

[Median duration of I = 13 mo]
54 pts
58 [24-77] 43% >60 yrs
57%M
I = 54 43%            
High dose I for no response to 400mg
N=20
5%         65%  
High dose I for cytogenetic relapse
N=34
38% 18% 20%        
Kantarjian, O'Brien, 200444

Includes patients from Kantarjian, Sawyers, et al., 20022, Karntarjian, Talpaz, et al., 200270 and Karntarjian, Talpaz, et al., 200371
400 mg

(increased to 800 mg for no CHR at 3 months, no MCR at 12 months, or relapse after CHR)

[34 mo for I; 109 mo for historical control]
Early CP:
I = 261 pts
34% >age 60;
Early CP
I = 261
73% 62% 11%     97% Estimated 2 yr OS from KM
I (early CP)= 95%
Historical control = 70%
Historical control = 204 pts
19% >age 60
Historical control = 204 24% 19 % (p<0.001) 5%     53%  
Late CP:
I = 147 pts
39% >age 60;
Late CP
I = 147
59% 41% 18% 10%   95%  
Historical control = 95 pts
9% >age 60
Historical control = 95 11% 7 % (p<0.001) 4% 13%   58%  
Historical controls = CML-CP treated w/ IFN based regimens from 1982-1997 whose disease progressed and were treated with some other subsequent therapy                
Karntarjian, Cortes, et al., 200472

Includes patients from Kantarjian, Sawyers, et al., 20022, Karntarjian, Talpaz, et al., 200270 and Karntarjian, Talpaz, et al., 200371
400 mg

(increased to 800 mg for no CHR at 3 months, no MCR at 12 months, or relapse after CHR)

[45 mo for I;
109 mo for historical control]
I = 261 pts
34% >age 60

Historical control = 251 pts
17% >age 60

Historical controls = CML-CP treated w/ IFN based regimens from 1982-1997 whose disease progressed and were treated with some other subsequent therapy

I=261


Historical control = 251

73%

63%

10%

5%
Major MR
43%
Complete MR
26%
Estimated K-M:

For imatinib:
4-yr OS = 86%
4-yr PFS = 80%

Major or Minor CR at 3 mo:
Yes -
4-yr PFS = 93%
4-yr OS = 95%
No -
4-yr PFS = 65%
4-yr OS = 78%
(p for both analyses <0.001)

For historical control:
4-yr PFS = 43%
Le Coutre, 200373 400 mg
[9mo]
39 pts
56 [23-80]
I = 39              
3 mo (N=33) 21% 6% 15%      
6 mo (N=27) 33% 30% 3%      
9 mo (N=13) 62% 62% 0%      
12 mo (N=3) 67% 33% 33%      
Marin, Goldman, et al., 200374 600-1000 mg
[416 days (212-790)]
36 pts (27 IFN refractory and 9 newly diagnosed)—all treated with higher dose I for failure to achieve CCR on I 400mg

age/gender not stated
I = 36 39% 19% 20%       Cytogenetic response short-lasting—43% with loss of response at med f/u (timeframe not clearly stated)
Marin, Marktel, Bua, et al., 200375 200-800 mg
[not stated]
145 pts
53 [17-76]
(>65 yr = 17%)
47%M

All IFN refractory; 14% received autoSCT
I = 145 29% 19%         12 mo OS = 87% (CI 92-80%)

24 mo OS = 63% (CI 78-56%)

12 mo PFS = 75% (CI 68-83%)

24 mo PFS = 52% (CI 47-60%)
Rosti, 20048 400mg
[26 mo]
191 pts
age/gender not stated
I = 191 61% 44%       89% At med f/u 26 mo, OS estimated from KM:
MCR achieved 97%
MCR not achieved 92%
   (p=0.037)
3 mo 41% 16%       89%
6 mo 44% 27%       89%
9 mo 42% 29%       86%
12 mo 48% 33%       80%

Abbreviations: * = abstract; CI = 95% confidence interval; CML = Chronic myelogenous leukemia; CP = chronic phase; CR = cytogenetic response; CCR = complete cytogenetic response; CHR = complete hematological response; CMR = complete molecular response; f/u = followup; I = Imatinib; IFN = Interferon; K-M = Kaplan-Meier; M = Male; MCR = major cytogenetic response; N = Number; OS = Overall Survival; PFS = progression-free survival; pt(s)=patient(s); RR = relative risk; SCT = Stem cell transplant

Return to Document
Proceed to Table 4

The information on this page is archived and provided for reference purposes only.

 

AHRQ Advancing Excellence in Health Care