. 2024 Jul 24;13(14):e70005. doi: 10.1002/cam4.70005

TABLE 1.

Characteristics of the 7 randomized clinical trials categorized into 8 groups.

Study name	Concurrent arm (con) versus nonconcurrent (non‐C) arm (N) ^a	Hormone receptor positive/total (%)	Cumulative dose of epirubicin (mg/m²)	T > 2 cm (%)	Node + (%)	UCG schedule	Definition of adverse cardiac events (ACE)	ACE rate	pCR rate
Buzdar MDACC 2005 ²⁴	Con: TH(4) → FECH(4) Non‐C: T(4) → FEC(4)	24/42 (57.14%)	300 300	91.3% 89.47%	56.52% 63.16%	Baseline, Q3M until the end of FEC	LVEF decrease >10%	30.43% 26.32%	66% 25%
CHER‐LOB ³⁴ , ³⁵	Con: wT(L)H(12) → FEC(L)H(4) Non‐C: wTL(12) → FECL(4)	73/121 (60.33%)	300 300	100% 100%	NR NR	Baseline, Q12W, completion	LVSD (CTCAE 3.0) > gr 1	1.22% 0%	37% 26%
GeparQuinto GBG 44 ³⁶ , ³⁷	Con: ECH(4) → DH(4) Non‐C: ECL(4) → DL(4)	341/615 (55.45%)	360 360	64.17% 65.58%	68.08% 67.53%	Baseline, Q4W, completion	Heart failure (CTCAE 4.03)	0.33% 2.27%	30% 23%
TRYPHAENA ²⁸ , ³¹ , ^b ^, ^c	Con: FECPH(3) → DPH(3) Non‐C: FEC(3) → DPH(3)	74/148 (50.00%)	300 300	100% 100%	73.97% 65.33%	Baseline, Q6W, completion, Q6M for 2 years, and then QY for 2 years	All‐grade LVSD (CTCAE 3.0)	9.59% 13.33%	51% 28%
TRYPHAENA ²⁸ , ³¹ , ^b ^, ^c	Con: FECPH(3) → DPH(3) Non‐C: DCarboPH(6)	79/150 (52.67%)	300 0	100% 100%	73.97% 68.83%	Baseline, Q6W, completion, Q6M for 2 years, and then QY for 2 years	All‐grade LVSD (CTCAE 3.0)	9.59% 10.39%	51% 40%
ACOSOG Z1041 ²⁷ , ³⁸	Con: wTH(12) → FECH(4) Non‐C: FEC(4) → wTH(12)	168/280 (60.00%)	300 300	92.96% 94.20%	63.38% 64.49%	Baseline, Q12W, Q24W	LVSD (CTCAE 3.0)	8.45% 3.62%	51% 51%
EORTC 10054 ²⁹	Con: DH(3) → FECH(3) Non‐C: DL(3) → FECL(3)	42/76 (55.26%)	300 300	100% 95.65%	67.92% 69.57%	Baseline, Q4W, completion	Absolute drop ≥15% in LVEF from baseline	0% 0%	51% 35%
TRAIN‐2 ³² , ³⁹ , ^c	Con: FECPH(3) → TCarboPH(6) Non‐C: TCarboPH(9)	255/438 (58.22%)	270 0	NR NR	62.56% 65.30%	Baseline, Q3M	LVEF decline of 10% or more AND LVEF <50%	8.68% 3.20%	64% 64%

Study name

Concurrent arm (con) versus nonconcurrent (non‐C) arm (N) ^a

Hormone receptor positive/total (%)

Cumulative dose of epirubicin (mg/m²)

T > 2 cm (%)

Node + (%)

UCG schedule

Definition of adverse cardiac events (ACE)

ACE rate

pCR rate

Buzdar MDACC 2005 ²⁴

Con: TH(4) → FECH(4)

Non‐C: T(4) → FEC(4)

24/42 (57.14%)

300

91.3%

89.47%

56.52%

63.16%

Baseline, Q3M until the end of FEC

LVEF decrease >10%

30.43%

26.32%

66%

25%

CHER‐LOB ³⁴ , ³⁵

Con: wT(L)H(12) → FEC(L)H(4)

Non‐C: wTL(12) → FECL(4)

73/121 (60.33%)

300

100%

Baseline, Q12W, completion

LVSD (CTCAE 3.0) > gr 1

1.22%

37%

26%

GeparQuinto GBG 44 ³⁶ , ³⁷

Con: ECH(4) → DH(4)

Non‐C: ECL(4) → DL(4)

341/615 (55.45%)

360

64.17%

65.58%

68.08%

67.53%

Baseline, Q4W, completion

Heart failure (CTCAE 4.03)

0.33%

2.27%

30%

23%

TRYPHAENA ²⁸ , ³¹ , ^b ^, ^c

Con: FECPH(3) → DPH(3)

Non‐C: FEC(3) → DPH(3)

74/148 (50.00%)

300

100%

73.97%

65.33%

Baseline, Q6W, completion, Q6M for 2 years, and then QY for 2 years

All‐grade LVSD (CTCAE 3.0)

9.59%

13.33%

51%

28%

TRYPHAENA ²⁸ , ³¹ , ^b ^, ^c

Con: FECPH(3) → DPH(3)

Non‐C: DCarboPH(6)

79/150 (52.67%)

300

100%

73.97%

68.83%

Baseline, Q6W, completion, Q6M for 2 years, and then QY for 2 years

All‐grade LVSD (CTCAE 3.0)

9.59%

10.39%

51%

40%

ACOSOG Z1041 ²⁷ , ³⁸

Con: wTH(12) → FECH(4)

Non‐C: FEC(4) → wTH(12)

168/280 (60.00%)

300

92.96%

94.20%

63.38%

64.49%

Baseline, Q12W, Q24W

LVSD (CTCAE 3.0)

8.45%

3.62%

51%

EORTC 10054 ²⁹

Con: DH(3) → FECH(3)

Non‐C: DL(3) → FECL(3)

42/76 (55.26%)

300

100%

95.65%

67.92%

69.57%

Baseline, Q4W, completion

Absolute drop ≥15% in LVEF from baseline

51%

35%

TRAIN‐2 ³² , ³⁹ , ^c

Con: FECPH(3) → TCarboPH(6)

Non‐C: TCarboPH(9)

255/438 (58.22%)

270

62.56%

65.30%

Baseline, Q3M

LVEF decline of 10% or more AND LVEF <50%

8.68%

3.20%

64%

Abbreviations: Con, concurrent arm; LVEF, left ventricular ejection fraction; LVSD, left ventricular systolic dysfunction; non‐C, nonconcurrent arm; NR, not reported; Q12W, every 12 weeks; Q3M, every 3 months; QY, annually; UCG, echocardiography.

^{^a}

Regimen abbreviations: T(H) paclitaxel (+ herceptin), FEC(H) fluorouracil + epirubicin + cyclophosphamide (+ herceptin), wT(L)H weekly paclitaxel + herceptin (+ lapatinib), D(H) docetaxel (+ herceptin), FECPH fluorouracil + epirubicin + cyclophosphamide + pertuzumab + herceptin, DPH docetaxel + pertuzumab + herceptin, DCarboPH docetaxel + carboplatin + pertuzumab + herceptin, TCarboPH paclitaxel + carboplatin + pertuzumab + herceptin.

^{^b}

TRYPHAENA was divided into two groups: concurrent arm versus nonconcurrent arm and concurrent arm versus non‐anthracycline arm.

^{^c}

The control arm of TRYPHAENA and TRAIN‐2 were anthracycline‐free regimens, which were considered of less cardiotoxicity.