Supplementary Table 1. Descriptive statistics of the unmatched study sample and analysis of the association between observed covariates and suspension/continuation of Trastuzumab treatment at disease progression.
Total sample† / Treatment continuation† / Treatmentsuspension† / Test statistic
(p-value)§
Total
/ 272 / 154 (56.6) / 118 (43.4)Patient-related variables
Age (years) / 53.4 (11.6) / 51.6 (11.6) / 55.7 (11.1) / -2.98 (0.0032)Menopause (n/y) / 184 (69.4) / 99 (65.1) / 85 (75.2) / 3.11 (0.0779)
Other tumors (n/y) / 9 (4.2) / 6 (4.4) / 3 (3.9) / 0.03 (0.8574)
LVEF (%) / 63.0 (6.2) / 63.2 (6.4) / 62.8 (5.8) / 0.38 (0.7069)
Patient status (live/dead) / 131 (48.2) / 63 (40.9) / 68 (57.6) / 7.48 (0.0062)
Tumor-related variables
ER status (neg/pos) / 133 (49.8) / 69 (45.1) / 64 (56.1) / 3.19 (0.0743)PgR status (neg/pos) / 104 (39.2) / 52 (34.4) / 52 (45.6) / 3.40 (0.0651)
Size (mm) / 12 (22.8) / 7.5 (13.9) / 17.8 (29.8) / 3.48 (0.0006)
Grade (I+II/III) / 160 (70.8) / 85 (68.5) / 75 (73.5) / 0.67 (0.4125)
Ductal histotype (n/y) / 196 (83.8) / 121 (83.4) / 75 (84.3) / 0.03 (0.8686)
N. of positive lymph nodes / 4 (8.5) / 4 (8) / 3.5 (8.5) / 0.38 (0.7036)
Disease status (ED/NED) / 14 (5.3) / 9 (5.9) / 5 (4.5) / 0.27 (0.6017)
Stadiation
T1 / 84 (33.9) / 42 (30.2) / 42 (38.5) / 1.93 (0.5880)
T2 / 114 (46.0) / 67 (48.2) / 47 (43.1)
T3 / 12 (4.8) / 7 (5) / 5 (4.6)
T4 / 38 (15.3) / 23 (16.5) / 15 (13.8)
HER2 score 2+ / 29 (10.9) / 18 (11.8) / 11 (9.6) / 0.36 (0.8363)
3+ / 211 (79.0) / 119 (78.3) / 92 (80.0)
Pos. / 27 (10.1) / 15 (9.9) / 12 (10.4)
Target+not target
metas. Visc. / 38 (14.0) / 13 (8.4) / 25 (21.2) / 13.87 (0.0010)
Not Visc. / 62 (22.8) / 30 (19.5) / 32 (27.1)
Other / 172 (63.2) / 111 (72.1) / 61 (51.7)
N. of metastatic lesions / 2 (2) / 2 (1) / 2 (2) / 2.57 (0.0102)
Surgery and therapies
Mastectomy (n/y) / 126 (56.8) / 73 (53.3) / 53 (62.4) / 1.76 (0.1849)
Quadrantectomy (n/y) / 94 (42.3) / 63 (46) / 31 (36.5) / 1.95 (0.1631)
Axillary dissection (n/y) / 171 (81.8) / 109 (84.5) / 62 (77.5) / 1.62 (0.2024)
N. of resected lymph nodes / 17 (10) / 18 (11) / 15 (8) / 2.08 (0.0372)
Radiotherapy (n/y) / 125 (46) / 74 (48.1) / 51 (43.2) / 0.63 (0.4281)
Neo-adjuvant therapy (n/y) / 53 (20.1) / 30 (20.0) / 23 (20.2) / 0.00 (0.9719)
Adjuvant therapy (n/y) / 224 (83.6) / 128 (84.2) / 96 (82.8) / 0.10 (0.7506)
Relapses and recurrences
Local relapse (n/y) / 40 (14.7) / 23 (14.9) / 17 (14.4) / 0.01 (0.903)
Controlateral relapse (n/y) / 13 (4.8) / 10 (6.5) / 3 (2.5) / 2.29 (0.1301)
Sovraclavear relapse (n/y) / 30 (11.0) / 17 (11.0) / 13 (11.0) / 0.00 (0.9954)
Distant metastases (n/y) / 248 (91.2) / 141 (91.6) / 107 (90.7) / 0.06 (0.7997)
Multiple metastases (n/y) / 194 (71.3) / 124 (80.5) / 70 (59.3) / 14.68 (0.0001)
Site of metastases - Lymph node / 8 (2.9) / 3 (1.9) / 5 (4.2) / - (0.007)
Liver / 30 (11) / 10 (6.5) / 20 (16.9)
Bone / 12 (4.4) / 5 (3.2) / 7 (5.9)
Lung / 15 (5.5) / 8 (5.2) / 7 (5.9)
CNS / 2 (0.7) / 0 (0) / 2 (1.7)
Skin / 6 (2.2) / 2 (1.3) / 4 (3.4)
Other / 199 (73.2) / 126 (81.8) / 73 (61.9)
N. of target lesions / 1 (1) / 2 (1) / 1 (1) / 3.2 (0.0014)
N. of not-target lesions / 1 (1) / 1 (1) / 1 (1) / -0.76 (0.45)
Site of metastases at first progression
Liver metastases (n/y) / 120 (44.1) / 63 (40.9) / 57 (48.3) / 1.48 (0.2234)Brain metastases (n/y) / 53 (19.5) / 33 (21.4) / 20 (16.9) / 0.85 (0.3553)
Trastuzumab treatment
Treatment schedule(1week / 3weeks) / 76 (28.5) / 50 (33.3) / 26 (22.2) / 3.99 (0.0459)
N. of cycles / 25.5 (21) / 33.6 (20.2) / 15.8 (17.6) / 7.55 (<0.0001)
Line of treatment (other/first) / 173 (65.8) / 94 (62.3) / 79 (70.5) / 1.96 (0.1615)
Monotherapy (n/y) / 9 (3.3) / 4 (2.6) / 5 (4.2) / 0.56 (0.4536)
Therapies associated to Trastuzumab
Taxane (n/y) / 153 (56.3) / 106 (68.8) / 47 (39.8) / 22.83 (<0.0001)Anthracycline (n/y) / 29 (10.7) / 19 (12.3) / 10 (8.5) / 1.05 (0.3063)
Platinum (n/y) / 33 (12.1) / 22 (14.3) / 11 (9.3) / 1.54 (0.214)
CMF (n/y) / 8 (2.9) / 5 (3.2) / 3 (2.5) / 0.12 (0.7333)
Vinorelbine (n/y) / 180 (66.2) / 104 (67.5) / 76 (64.4) / 0.29 (0.5892)
Capecitabine (n/y) / 46 (16.9) / 30 (19.5) / 16 (13.6) / 1.67 (0.1967)
Tamoxifen (n/y) / 18 (6.6) / 8 (5.2) / 10 (8.5) / 1.16 (0.2809)
Aromatase inhibitor (n/y) / 34 (12.5) / 24 (15.6) / 10 (8.5) / 3.09 (0.0789)
Gemcitabine (n/y) / 23 (8.5) / 22 (14.3) / 1 (.8) / - (<0.0001)
Other drugs (n/y) / 23 (8.5) / 15 (9.7) / 8 (6.8) / 0.76 (0.3844)
End-points analyses
Time from diagnosis of primary tumor to progression (months) / 23 (28) / 20 (26) / 27 (32) / -2.42 (0.0156)
Time from diagnosis of primary tumor to first Trastuzumab treatment / 29 (36) / 26 (32) / 35 (42) / -1.62 (0.1056)
Patient response to first line Trastuzumab-based therapy (No resp./Resp.) / 123 (45.2) / 79 (51.3) / 44 (37.3) / 5.29 (0.0214)
† Descriptive statistics. Continuous covariates: mean and (sd). Counts: median and (interquartile range). Categorical covariates: absolute frequency and (relative frequency).
§ Test of independence between covariates and discontinuation/continuation of Trastuzumab treatment at progression. Continuous covariates: t-test statistic and (p-value). Counts: ranksum statistic and (p-value). Categorical covariates: chi-square statistic and (p-value) or Fisher’s exact test when the absolute frequency of one or more classes is less than 5.
Supplemetary Fig. 1. Estimation of covariates’ variable importance for the outcome variable “continuation/suspension of treatment after disease progression”.
Supplemetary Fig. 2. Estimation of covariates’ variable importance for the outcome variable “patient survival”.
Supplementary table 2 Propensity score calculation using a logistic model. Odds ratios, 95% confidence intervals and p-values of the estimated model.
Odds ratio / 95% CI / pTaxane / 0.46 / 0.26 / 0.80 / 0.007
N. of resected lymph nodes / 0.96 / 0.91 / 1.00 / 0.053
Axillary dissection / 0.46 / 0.24 / 0.90 / 0.025
Size of first metastatic lesion at progression (mm) / 1.02 / 1.01 / 1.04 / 0.012
RECIST response to first-line trastuzumab-based therapy / 0.65 / 0.37 / 1.16 / 0.149
Multiple metastases / 0.30 / 0.16 / 1.57 / <0.001
Gemcitabine / 0.07 / 0.00 / 0.34 / 0.010
Time from diagnosis of primary tumor to progression (months) / 1.00 / 0.99 / 1.01 / 0.481
Target/not target metastases
Not Visceral / 0.22 / 0.01 / 2.40 / 0.272
Other / 0.17 / 0.01 / 1.81 / 0.198
Age / 1.02 / 0.99 / 1.04 / 0.258
Site of metastasis:
Bone / 0.63 / 0.13 / 3.09 / 0.564
Lung / 0.79 / 0.18 / 3.43 / 0.751
Other / 1.26 / 0.32 / 5.24 / 0.747
Aromatase inhibitor / 0.68 / 0.26 / 1.67 / 0.408
N. of positive lymph nodes
/ 0.97 / 0.92 / 1.03 / 0.338N. of target lesions / 0.87 / 0.64 / 1.17 / 0.374