LVEF, Left Ventricular Ejection Fraction

Figure S1: Algorithm for continuation and discontinuation of pertuzumab/placebo and trastuzumab based on LVEF assessments

LVEF, left ventricular ejection fraction

Figure S2: CONSORT diagram

Table S1: Cardiac medication for symptomatic LVSD
Placebo
+ trastuzumab
+ docetaxel / Pertuzumab
+ trastuzumab
+ docetaxel
Patients with symptomatic LVSD, n / 7 / 4
Patients with at least one treatment, n
Loop diuretics / 6 / 4
Cardiac glycosides / 1 / 2
Beta-adrenoceptor blocking agents / 1 / 3
Angiotensin-converting enzyme inhibitors / 0 / 3
Bronchodilators and antiasthmatics / 1 / 1
Anticoagulants / 1 / 1
Oxygen / 1 / 1
Spironolactone / 0 / 2
Paracetamol / 1 / 0
Losartan / 1 / 0
Ferrous sulfate / 1 / 0
Metoclopramide / 1 / 0
Nifedipine / 1 / 0
Prednisone / 1 / 0
Dipyrone / 0 / 2
Aspirin / 0 / 1
Ubidecarenone / 1 / 0
Respiratory therapy / 1 / 0
Hydrochlorothiazide / 1 / 0
Omeprazole / 0 / 1
Dobutamine / 0 / 1
Sodium nitroprusside / 0 / 1
Total number of patients with at least one treatment / 6 / 4
LVSD, left ventricular systolic dysfunction
Table S2: Univariate Cox regression of LVSD (all grades)
Covariate effect* / Treatment effect adjusted for covariate†
Effect/covariate / Patients, n / HR / 95% CI / p-value / HR / 95% CI / p-value
Ptz+T+D vs Pla+T+D / 804 / 0.42 / 0.24–0.76 / 0.0036
Exposure to prior anthracyclinesvs no exposure / 804 / 2.21 / 1.27–3.86 / 0.0053 / 0.44 / 0.25–0.78 / 0.0053
Prior radiotherapy vs no radiotherapy / 804 / 2.43 / 1.37–4.31 / 0.0025 / 0.43 / 0.24–0.77 / 0.0045
Prior trastuzumab treatment vs no treatment / 804 / 1.47 / 0.66–3.26 / 0.3459 / 0.42 / 0.24–0.75 / 0.0035
Age group: ≥65 years vs <65 years / 804 / 1.25 / 0.61–2.56 / 0.5502 / 0.42 / 0.24–0.75 / 0.0034
Age group: ≥75 years vs <75 years / 804 / 2.25 / 0.55–9.29 / 0.2606 / 0.43 / 0.24–0.77 / 0.0042
Smoking status
Past smoker vs never smoked
Current smoker vs never smoked / 804
804 / 1.69
0.94 / 0.81–3.50
0.34–2.65 / 0.1587
0.9122 / 0.43 / 0.24–0.76 / 0.0038
Diabetic vs non-diabetic / 804 / 0.60 / 0.19–1.91 / 0.3840 / 0.43 / 0.24–0.77 / 0.0042
Hypertensive vs non-hypertensive / 804 / 0.91 / 0.49–1.71 / 0.7750 / 0.42 / 0.24–0.75 / 0.0034
D, docetaxel; LVSD, left ventricular systolic dysfunction; Pla, placebo; Ptz, pertuzumab; T, trastuzumab
* Model that includes only the covariate
† Model that includes the covariate and treatment
51 patients developed LVSD (NCI-CTCAE grades 1–5): 33 patients in the placebo arm and 18 patients in the pertuzumab arm.