Metronomic chemotherapy for non-metastatic triple negative breast cancer: Selection is the key

Table 4 Maintenance for triple negative breast cancer

	IBCSG Trial 22, Oct. 2016	CREATE-X trial, 2015
Study design	Phase III	Phase III
Accrual time	2000-2012	2007-2012
Number of patients	N: 1086 CM: 542 Obs: 539	N: 910 X: 455 Obs: 455
Setting	Prior adjuvant ± RT	Prior neoadyuvant ± RT
Study population	TNBC: 75% HER2+: 19%	Luminal or TNBC No pCR o node positive
Previous treatment	A + CMF: 60% CMF: 16% AT sequential + CMF: 26% H: 59% (of HER2+)	A: 4.1% AT sequential: 81% AT concurrently: 13.6% TC: 5%
Study treatment	C 50 mg/d PO Daily M 2.5 mg bid PO Days 1-2 vs Observation	X 1250 mg/m2 twice/d PO Day 1-14 Observation
Time of treatment	Every week for 1 yr	Every 3 wk for 8 cycles (6 mo)
DFS	5 yr DFS: CM: 78.1% Obs: 74% HR = 0.84 (95%CI: 0.66 to 1.06; P = 0.14) TNBC: n = 814; HR = 0.80; 95%CI: 0.60-1.06 TNBC, node-positive disease: n = 340; HR = 0.72; 95%CI: 0.49-1.05	5 yr DFS: X: 74.1% Obs: 67.7% HR (95%CI): 0.70 (0.53-0.93); P = 0.00524 30% reduction in risk
OS	No results	5 yr OS X: 89.2% Obs: 83.9%, P < 0.01
Adverse events	Hipertransaminasemia G3-G4: 7% Leukopenia: 2%	X: HFS G3: 10.9% Neutropenia G3: 6.6% Diarrhea G3: 3% Obs: Neutropenia 1.6% Diarrhea: 0.4%

C: Cyclophosmide; M: Methotrexate; X: Capecitabine; ER: Estrogen receptor; PR: Progesterone receptor; A: Anthracycline; F: 5Fluoracil; T: Taxane; TNBC: Triple negative breast cancer; H: Herceptin.