Table 2.

Studies Evaluating Use of Specific Second- or Third-Generation TKIs in the Third-Line Setting and Beyond

Reference	Patient Population (Disease State at Start of Study Drug)	Prior TKI(s)	Treatment (Starting Dose Used in Study) and Setting	Duration of Follow-up (Since Start of Study Drug)	Key Efficacy Outcomes
Second-Generation TKIs
Garg et al 200935	CML (N=48) CP-CML (n=25) AP-CML (n=10) BP-CML (n=13)	Imatinib → nilotinib (n=34) Imatinib → dasatinib (n=14)	Dasatinib (50–140 mg qd or 50–120 mg bid; n=34) or nilotinib (400–800 mg qd or 400 mg bid; n=14) in third-line setting	Median, 13 mo (range, 0.5–41)	CHR: 76%, CP; 90%, AP; 46%,a BP MCyRb: 40%, CP; 40%, AP; 31%, BP CCyRb: 32%, CP; 20%, AP; 23%, BP MMR: 20%, CP; 10%, AP; 8%, BP Median EFS: 13 mo Median FFS: 5 mo (20 mo, CP; 5 mo, AP; 3 mo, BP) Median OS: 20 mo
Nicolini et al 200936	CML (N=292) CP-CML (n=218) AP-CML (n=34) BP-CML (n=40)	Imatinib → dasatinib (n=292)	Nilotinib (400 mg bid) in third-line setting	Not reported; median exposure, 7 mo (range, 0.1–25)	CHR: 40%, CP; 10%, AP; 3%, BP MCyR: 41%, CP; 7%, AP; 14%, BP CCyR: 28%, CP
Giles et al 201037	CML (N=54) CP-CML (n=37) AP-CML (n=17)	Imatinib → dasatinib (n=54)	Nilotinib (400 mg bid) in third-line setting	Median, 12 mo	CHR: 79%,c CP; 29%, AP MCyR: 43%, CP; 12%, AP CCyR: 24%, CP; 0%, AP 18-mo PFS: 59%, CP 18-mo OS: 86%, CP
Ibrahim et al 201038	CP-CML (N=26)	Imatinib → nilotinib (n=6) Imatinib → dasatinib (n=20)	Dasatinib (standard doses; n=6) or nilotinib (standard doses; n=20) in third-line setting	Median, 22 mo (range, 6–47)	MCyR: 50% CCyR: 35% MMR: 19% 30-mo EFS: 46% 30-mo OS: 47%
Khoury et al 201239	CP-CML (N=118)	Imatinib → nilotinib (n=28) Imatinib → dasatinib (n=87) Imatinib → dasatinib → nilotinib (or imatinib → nilotinib → dasatinib) (n=3)	Bosutinib (500 mg qd) in third-line setting (n=115) or fourth-line setting (n=3)	Median, 29 mo (range, 0.3–56)	CHR: 65%d MCyR: 32% CCyR: 24% MMR: 15% 1-y PFS: 77% 2-y PFS: 73% 1-y OS: 91% 2-y OS: 83%
Russo Rossi et al 201340	CML (N=82) CP-CML (n=68) AP-CML (n=9) BP-CML (n=5)	Imatinib → nilotinib (n=34) Imatinib → dasatinib (n=48)	Dasatinib (dose not specified; n=34) or nilotinib (dose not specified; n=48) in third-line setting	Median, 14 mo (range, 2–37)	CHR: 85% MCyR: 48%b CCyR: 33%b MMR: 16%
Third-Generation TKI
Cortes et al 201341 Cortes et al 201442	CML or Ph+ ALL (N=449) CP-CML (n=270) AP-CML (n=85) BP-CML (n=62) Ph+ ALL (n=32)	93% received ≥2 prior approved TKIs (imatinib, dasatinib, nilotinib, or bosutinib); 55% received ≥3; 444 were resistant or intolerant to dasatinib or nilotinib, or had the T315I mutatione	Ponatinib (45 mg qd) in second-, third-, fourth-, or fifth-line setting (considering prior approved TKIs only)	Median, 28 mo (range, 0.1–40)	CP-CMLe: MCyR: 59% CCyR: 53% MMR: 38% 2-y PFS: 67% 2-y OS: 86% AP-CMLe: MaHR: 61% 2-y OS: 72% BP-CML: MaHR: 31% 2-y OS: 18% Ph+ ALL: MaHR: 41% 2-y OS: 18%

Abbreviations: ALL = acute lymphoblastic leukemia; AP = accelerated phase; bid = twice daily; BP = blast phase; CCyR = complete cytogenetic response; CHR = complete hematologic response; CML = chronic myeloid leukemia; CP = chronic phase; EFS = event-free survival; FFS = failure-free survival; MaHR = major hematologic response; MCyR = major cytogenetic response; MMR = major molecular response; OS = overall survival; PFS = progression-free survival; Ph+ = Philadelphia chromosome–positive; qd = once daily; TKI = tyrosine kinase inhibitor.

^aRate includes return to CP.

^bStudy reported best responses; lesser responses are included.

^cRate is among 28 patients without CHR at baseline.

^dRate is among 68 patients without CHR at baseline.

^eFive patients with a history of the T315I mutation but no T315I mutation detected at baseline (3 CP-CML; 2 AP-CML) were excluded from the efficacy population.