Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial

Figures & data

Table 1 Minimum Acceptable Regimens for Chemotherapy for Participation in Previous Trials

Type of Regimen	Regimens
Anthracyclines (A or E combined with C, with or without F) without taxanes, taxanes combined with C^Citation16,Citation17	Initial minimum permitted dose of E is from 75 to 100 mg/m^2, and the dose of A is 50 mg/m^2. The dose for EC is 90 mg/m^2, and that for FEC/CEF is 90–100 mg/m^2 (administered every 21 days). The dose for D is 75 mg/m^2
Anthracyclines (with or without C and/or F) and taxanes administered sequentially^Citation17–20	Initial minimum dose for injection of A is 60 mg/m^2 (50 mg/m^2 is also accepted for A in regimens of FAC). The dose for E is 90 mg/m^2 (75 mg/m^2 is also accepted for E in regimens such as FEC). The dose for P is 175 mg/m^2 (75 mg/m^2 or 100 mg/m^2 every 7 days for 8 doses; or 80 mg/m^2 every 7 days for 12 doses). The dose for D is 100 mg/m^2 or 75 mg/m^2
Anthracyclines are administered (with or without C) together with taxanes^Citation20,Citation21	Initial minimum dose for injection of A is 50 mg/m^2. The dose for E is 75 mg/m^2. The dose for P is 135 mg/m^2. The dose for D is 60 mg/m^2 or 75 mg/m^2

Notes: A, doxorubicin; E, epirubicin; C, cyclophosphamide; T, Paclitaxel (P) or docetaxel (D); M, methotrexate; F, 5-fluorouracil.

Table 2 Baseline Characteristics of the SYSUCC-001 Trial

Variables	Capecitabine Group (N=221), n (%)	Observation Group (N=213), n (%)	P-value*
Neo/adjuvant chemotherapy regimens			0.839
Non-anthracycline-taxane	2 (0.9)	1 (0.5)
Anthracycline	1 (0.5)	2 (0.9)
Taxane	20 (9.0)	22 (10.3)
Anthracyclines-taxane	198 (89.6)	188 (88.3)
Neo/adjuvant chemotherapy dose
Anthracycline dose			0.141
Consistent	57 (25.8)	69 (32.4)
Inconsistent	142 (64.3)	122 (57.3)
NA	22 (10.0)	22 (10.3)
Taxane dose			>0.99
Consistent	113 (51.1)	110 (51.6)
Inconsistent	104 (47.1)	100 (46.9)
NA	4 (1.8)	3 (1.4)

Note: *Ignoring missing values.

Abbreviation: NA, non-anthracycline or non-taxane.

Table 3 Subgroup Analysis of DSM in Capecitabine Group and Observation Group According to Doses

Variables	Capecitabine Group (N=221)				Observation Group (N=213)
	N	DSM (%)	HR^a	HR^b	N	DSM (%)	HR^a	HR^b
Anthracycline dose
Consistent	57	15 (36.2)	Ref	Ref	69	23 (33.3)	Ref	Ref
Inconsistent	142	20 (14.1)	0.51 (0.26–1.0)	0.65 (0.32–1.33)	122	27 (22.1)	0.67 (0.38–1.16)	0.66 (0.37–1.20)
Taxane dose
Consistent	113	15 (13.3)	Ref	Ref	110	35 (31.8)	Ref	Ref
Inconsistent	104	23 (22.1)	1.75 (0.91–3.35)	2.04 (1.02–4.06)	100	21 (21.0)	0.60 (0.35–1.04)	0.73 (0.42–1.29)

Notes: ^aUnivariate analysis; ^bMultivariate analysis corrected for other baseline information.

Abbreviation: DSM, disease-specific mortality; HR, hazard ratio.

Table 4 Interactive Analysis of DSM in Capecitabine Group and Observation Group According to Regimen Dose Standard

Subgroup	DSM No./total No.		HR (95%CI)	P interaction
	Capecitabine	Observation
Anthracycline dose
Consistent	15/57	23/69	0.80 (0.42–1.53)	0.552
Inconsistent	20/142	27/122	0.62 (0.35–1.10)
NA	3/22	6/22
Taxane dose
Consistent	15/113	35/110	0.38 (0.21–0.70)	0.014*
Inconsistent	23/104	21/100	1.09 (0.61–1.98)
NA	0/4	0/3
Anthracycline-taxane dose
Consistent	7/27	12/27	0.54 (0.21–1.37)	0.693
Inconsistent	28/170	38/162	0.69 (0.42–1.12)
NA	3/24	6/24

Note: *P<0.05.

Abbreviations: DSM, disease-specific mortality; CI, confidence interval; NA, non-anthracycline or non-taxane.

Figure 1 Cumulative hazard divided by taxane dose in the capecitabine group and observation group. Median observation for all curves was 61 months (interquartile range, 44–82 months). Cumulative hazards were estimated using Kaplan–Meier analysis and compared using log rank tests. Hazard ratios with 95% confidence intervals were estimated using a Cox proportional hazards model.

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