copyright © 2011 research to practice. all rights reserved. interest in topics related to the...

Copyright © 2011 Research To Practice. All rights reserved.

Interest in Topics Related to the Treatment of Patients with CML (Percent Responding 9 or 10)

36%

36%

38%

38%

39%

42%

32% 34% 36% 38% 40% 42% 44%

Resistance mutations in BCR-ABL

Monitoring patients during therapy

New agents/regimens

Sequencing of TKIs

TKI-refractory CML

Efficacy and tolerability of TKIs*

*Tyrosine kinase inhibitors: Imatinib, dasatinib, nilotinib

Chronic Myeloid Leukemia (CML)

Susan M O’Brien, MD

IRIS 8-Year Update: Outcome After Imatinib

37%

Deininger M et al; Blood 2009;114(22):462.

Nilotinib vs Imatinib in Newly Dx CML (ENESTnd)

• Primary endpoint: MMR at 12 months

• Key secondary endpoint: Durable MMR at 24 months

• Other endpoints: CCyR by 12 months, time to MMR and CCyR, EFS, PFS, time to AP/BC on

study treatment, OS including follow-up

*Stratification by Sokal risk score

Imatinib 400 mg QD (n = 283)

Nilotinib 300 mg BID (n = 282)

RANDOMIZED*

Nilotinib 400 mg BID (n = 281)

• N = 846

• 217 centers

• 35 countries

Follow-up 5 years

Hughes et al. ASH 2010; abst #207

Nilotinib vs Imatinib in Newly Dx CML-CP (ENESTnd). Primary Endpoint - MMR Rate at 12 Months (ITT Population)

P < .0001

P < .0001

Pat

ien

ts w

ith

MM

R (

%)

Larson RA et al. J Clin Oncol 2010;28; Abstract 6501. Saglio G et al. N Engl J Med 2010;362; Abstract 2251.

IRIS 8-Year Results: Annual Rate of Events on Imatinib

• EFS = 81%• Freedom from progression to AP/BC = 92%-1 progression to AP/BC and 2 non-CML related deaths in year 8

Deininger et al. ASH 2009. Abs # 1126.

3.3

7.5

4.8

1.7

0.80.3

1.4 1.31.5

2.8

1.8

0.90.5

0 00.4

0

1

2

3

4

5

6

7

8

1 2 3 4 5 6 7 8

Year

EventLoss of C HR,Loss of MCyR,AP/BC ,Death during treat

AP/BCAP/BC

% W

ith C

CyR

Dasatinib versus Imatinib Study in Treatment-Naïve CML: DASISION (CA180-056) Study Design

● Primary endpoint: Confirmed CCyR by 12 months

● Secondary/other endpoints: Rates of CCyR and MMR; times to confirmed CCyR, CCyR and MMR; time in confirmed CCyR and CCyR; PFS; overall survival

Follow-up

5 yearsRandomized*

Imatinib 400 mg QD (n = 260)

Dasatinib 100 mg QD (n = 259)• N = 519

• 108 centers

• 26 countries

*Stratified by Hasford risk score

Shah et al. ASH 2010; abst #206.

DASISION: First-Line Dasatinib vs Imatinib in CML-CP CCyR Rate by 12 Months (ITT)

8377

7266

0

20

40

60

80

100

Dasatinib100 mg QD

Imatinib400 mg QDCCyR

(%)

Confirmed CCyRby 12 months

CCyRby 12 months

P = 0.0011P = 0.0067

Kantarjian. N Engl J Med 362: 2260, 2010.

DASISION: Progression to AP-BP (ITT)

• No patient who achieved MMR progressed to AP/BP CML

• 5 patients who achieved a CCyR progressed to AP/BP CML (2 dasatinib, 3 imatinib)

• Rates of progression-free survival at 18 mos: 94.9% for dasatinib and 93.7% for imatinib

2.3

3.5

0

2

4

6

Progressed to AP/BP, %

Dasatinib 100 mg QD

Imatinib 400 mg QD

n/N 6/259 9/260

Shah N et al. Blood 2010;116: Abstract 206.

100

DASISION: Confirmed CCyR (ITT)


P = 0.0086 P = 0.0366

77 7867 70

0

20

40

60

80

100

12 Months 18 Months

Confirmed CCyR, %

Dasatinib100 mg QD

Imatinib 400mg QD

Definitions of PFS-EFS in CMLDefinitions of PFS-EFS in CML

• Definitions of EFS/PFS vary in different studies• Definitions applied to 435 pts treated with frontline TKI

OccurrenceEFS-IRIS

TWP-ENEST

PFS-DASISION

EFS-MDACC

AP-BP on TKI + + + +

off TKI - - - +

Death on TKI +CML-related <30 d off TKI

Any cause +

off TKI -CML-related <30 d off TKI

<60 d off TKI +

Loss of CHR/MCyR + - + (also ↑WBC) +

• EFS-MDACC accounts for any event off TKI and any death on/off TKI

Kantarjian et al. Blood 2010:116; Abst #672.

Outcome According to Different Definitions of EFS/PFS

Kantarjian et al. Blood 2010:116;Abst #672.

Definitions Event 5-yr (%)

ENEST-TWP 15 96

IRIS-EFS 40 90

DASISION-PFS 43 89

MDACC-EFS 82 81

- Because EFS and PFS are important in determining whether new TKIs are better than imatinib in front-line therapy, precise and common definitions of these endpoints are needed.

- Because EFS and PFS are important in determining whether new TKIs are better than imatinib in front-line therapy, precise and common definitions of these endpoints are needed.

Data cut-off: 20Aug2010Hughes TP, et al. ASH 2010. Abstract 207.

DASISION: Grade 3/4 Cytopenia

11

2219

7

20

10

0

20

40

60

Anemia Neutropenia Thrombocytopenia

Patients, %

Dasatinib 100 mg QD

Imatinib 400 mg QD

100

• Grade 3/4 bleeding occurred in 2 patients on dasatinib and 3 patients on imatinib

• 6 patients on dasatinib and 3 patients on imatinib D/C Rx due to cytopenia


Common Nonhematologic Drug-Related AEs (≥10%)

AE, %Dasatinib 100 mg QD

N = 258Imatinib 400 mg QD

N = 258

All Grades Grade 3/4 All Grades Grade 3/4

Fluid retention 23 1 43 1

Superficial edema* 10 0 36 <1

Pleural effusion 12 <1 0 0

Myalgia† 22 0 38 1

Nausea 9 0 21 0

Vomiting 5 0 10 0

Diarrhea 18 <1 19 1

Fatigue 8 <1 11 0

Headache 12 0 10 0

Rash 11 0 17 1

* Includes 11 MedDRA preferred terms† Includes myalgia, muscle inflammation and musculoskeletal pain


What Clinicians Want to Know

A Live CME Event Addressing the Most Common Questions and Controversies in the Current Clinical

Management of Select Hematologic Cancers

Sunday, June 5, 20117:00 PM – 9:30 PMChicago, Illinois

Faculty

Sergio Giralt, MDJohn P Leonard, MD Lauren C Pinter-Brown, MD

ModeratorNeil Love, MD

Antonio Palumbo, MDSusan M O’Brien, MDProfessor Michael Hallek


What is your preferred initial systemic treatment for chronic-phase CML?

2%

4%

20%

10%

4%

11%

47%

0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50%

Other

Nilotinib 400 mg twice daily

Nilotinib 300 mg twice daily

Dasatinib 100 mg daily

Imatinib 800 mg daily




Have you discontinued imatinib, dasatinib or nilotinib for patients responding with sustained molecular CR?

3%

4%

10%

82%

0% 20% 40% 60% 80% 100%

Yes, other

Yes, after 5years

Yes, after 2years

No


What Clinicians Want to Know

A Live CME Event Addressing the Most Common Questions and Controversies in the Current Clinical

Management of Select Hematologic Cancers

Sunday, June 5, 20117:00 PM – 9:30 PMChicago, Illinois

Faculty

Sergio Giralt, MDJohn P Leonard, MD Lauren C Pinter-Brown, MD

ModeratorNeil Love, MD

Antonio Palumbo, MDSusan M O’Brien, MDProfessor Michael Hallek

copyright © 2011 research to practice. all rights reserved. interest in topics related to the...

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