Long-term safety and efficacy of dasatinib in the treatment of chronic-phase chronic myeloid leukemia patients resistant or intolerant to imatinib

Figures & data

Table 1 Characteristics of clinical trials evaluating efficacy and safety of dasatinib as a second-line treatment in imatinib-resistant or -intolerant CML-CP

Trial	CAI80-002^Citation26,Citation28	START-C^Citation29^–^Citation31	START-R^Citation35,Citation36	CAI80-034^Citation37^–^Citation40
Study design	Phase I	Phase II	Phase II	Phase III
Treatment schedule	15–180 mg (QD or BID)	70 mg (BID)	70 mg (BID)	100 mg QD or
				50 mg BID or
				140 mg QD or
				70 mg BID
Number of patients (CML-CP)	n=40	n=387	n=101	n=662
Follow-up	27 months	24 months	24 months	72 months

Abbreviations: BID, twice daily; CML-CP, chronic phase-chronic myeloid leukemia; QD, once daily; START-C, SRC/ABL Tyrosine Kinase Inhibition Activity: Research Trials of Dasatinib; START-R, START randomized trial.

Table 2 Long-term efficacy of dasatinib as a second-line treatment in chronic phase CML patients with resistance or intolerance to imatinib

	CAI80-002^Citation26,Citation28	START-C^Citation29^–^Citation31	START-R^Citation35,Citation36	CAI80-034^Citation37^–^Citation40,Table Footnotea
MHR	91%	91%	93%	NA
MCyR	51%	62%	53%	59%
CCyR	44%	53%	44%	41%
MMR	NA	47%	29%	43%
PFS	87%^b/28%^c	80%	86%	49%
OS	94%^b/68%^c	94%	NA	71%
Time point of analysis	27/36 months	24 months	24 months	72 months

Notes:

a Data shown for patients treated in the 100 mg QD cohort (n=167);

b analysis after 36 months, PFS and OS for patients that achieved a MCyR during the first year of treatment;

c analysis after 36 months, PFS and OS for patients that did not achieve a MCyR during the first year of treatment.

Abbreviations: CCyR, complete cytogenetic response; CML, chronic myeloid leukemia; MCyR, major cytogenetic response; MHR, major hematological response; MMR, major molecular response; NA, not available; OS, overall survival; PFS, progression-free survival; QD, once daily; START-C, SRC/ABL Tyrosine Kinase Inhibition Activity: Research Trials of Dasatinib in Chronic Phase Patients; START-R, START randomized trial.

Table 3 Dasatinib-related hematological adverse events in CML-CP after imatinib failure

	CAI80-002^Citation26,Citation28	START-C^Citation29^–^Citation31	START-R^Citation35^–^Citation36	CAI80-034^Citation37^–^Citation40
Dosing schedule	15–180 mg (QD or BID)	70 mg (BID)	70 mg (BID)	100 mg (QD)
Grade	Grade 3/4	Grade 3/4	Grade 3/4	Grade 3/4
Anemia	NA	22%^b	20%	13%
Leukocytopenia	NA	27%^b	24%	18%
Neutropenia	45%^a	50%^c	63%	36%
Thrombocytopenia	35%^a	49%^c	57%	24%

Notes:

a Data after a median follow-up of 12 months;

b data after a median follow-up of 15.2 months;

c data after a 24-month follow-up.

Abbreviations: BID, twice daily; CML-CP, chronic-phase chronic myeloid leukemia; NA, not available; QD, once daily; START-C, SRC/ABL Tyrosine Kinase Inhibition Activity: Research Trials of Dasatinib in Chronic Phase Patients; START-R, START randomized trial.

Table 4 Dasatinib-related nonhematological adverse events in CML-CP after imatinib failure

	CAI80-002^Citation26,Citation28		START-C^Citation29^–^Citation32		START-R^Citation35,Citation36		CAI80-034^Citation37^–^Citation40
Dosing schedule	15-180 mg daily (QD or BID)		70 mg daily (BID)		70 mg daily (BID)		100 mg daily (QD)
Follow-up	12 months		15.2/24 months		24 months		72 months
Grade	All grades	Grade 3/4	All grades^a	Grade 3/4	All grades	Grade 3/4	All grades	Grade 3/4
Pleural effusion	13%	0	27%	9%^b	25%	5%	25%	5%
Peripheral edema	18%	0	18%	0	20%	1%	26%	1%
Dyspnea	10%	0	30%	6%^b	23%	5%	33%	2%
Abdominal pain	NA	NA	NA	NA	15%	0	24%	3%
Hemorrhage	NA	NA	NA	4%^b	18%	1%	25%	3%
Fever	NA	NA	16%	1%	14%	0	NA	NA
Infection	NA	NA	NA	NA	14%	4%	47%	6%
Diarrhea	18%	0	37%	3%^b	37%	3%	41%	4%
Asthenia	NA	NA	14%	1%	15%	0	NA	NA
Nausea	5%	0	25%	1%	24%	0	22%	1%
Vomiting	0	0	11%	0.5%	10%	0	NA	NA
Fatigue	8%	2%	31%	3%^b	33%	3%	37%	4%
Headache	10%	0	32%	1%	26%	2%	47%	1%
Skin rash	2%	0	26%	0.5%	18%	0	33%	2%
Musculoskeletal pain	NA	NA	NA	NA	21%	1%	49%	3%

Notes:

a Data for “all grades” after a median follow-up of 15.2 months;

b data from a 24-month follow-up presented as an abstract at the 2008 American Society of Clinical Oncology Annual Meeting.³¹

Abbreviations: BID, twice daily; CML-CP, chronic-phase chronic myeloid leukemia; NA, not available; QD, once daily; START-C, SRC/ABL Tyrosine Kinase Inhibition Activity: Research Trials of Dasatinib in Chronic Phase Patients; START-R, START randomized trial.

Talpaz M, Shah NP, Kantarjian H, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med. 2006;354(24):2531–2541.

 PubMed Web of Science ®Google Scholar

Cortes J, Sawyers CL, Kantarjian HM, et al. Long-term efficacy of dasatinib in chronic-phase CML: results from the Phase I trial (CA180002). Blood. (ASH Annual Meeting Abstracts) 2007;110(11): Abstract 1026.

 Google Scholar

Hochhaus A, Baccarani M, Deininger M, et al. Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. Leukemia. 2008;22(6):1200–1206.

 PubMed Web of Science ®Google Scholar

Mauro MJ, Baccarani M, Cervantes F, et al. Dasatinib 2-year efficacy in patients with chronic-phase chronic myelogenous leukemia (CML-CP) with resistance or intolerance to imatinib (START-C). J Clin Oncol. 2008;26(Suppl 15): Abstract 7009.

 Web of Science ®Google Scholar

Kantarjian H, Pasquini R, Hamerschlak N, et al. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial. Blood. 2007;109(12):5143–5150.

 PubMed Web of Science ®Google Scholar

Kantarjian HM, Pasquini R, Lévy V, et al. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia resistant to imatinib at a dose of 400 to 600 milligrams daily: two-year follow-up of a randomized phase 2 study (START-R). Cancer. 2009;115(18):4136–4147.

 PubMed Web of Science ®Google Scholar

Shah NP, Kim DW, Kantarjian H, et al. Potent, transient inhibition of BCR–ABL with dasatinib 100 mg daily achieves rapid and durable cytogenetic responses and high transformation-free survival rates in chronic phase chronic myeloid leukemia patients with resistance, suboptimal response or intolerance to imatinib. Haematologica. 2010;95(2):232–240.

 PubMed Web of Science ®Google Scholar

Shah NP, Guilhot F, Cortes JE, et al. Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: follow-up of a phase 3 study. Blood. 2014;123(15):2317–2324.

 PubMed Web of Science ®Google Scholar

Apperley JF, Cortes JE, Kim DW, et al. Dasatinib in the treatment of chronic myeloid leukemia in accelerated phase after imatinib failure: the START a trial. J Clin Oncol. 2009;27(21):3472–3479.

 PubMed Web of Science ®Google Scholar