supplementary online content - jama...supplementary online content dang ct, guo h, najita j, et al....

Supplementary Online Content

Dang CT, Guo H, Najita J, et al. Cardiac outcomes of patients receiving adjuvant weekly paclitaxel and trastuzumab for node-negative, ERBB2-positive breast cancer. JAMA Oncol. Published online November 5, 2015. doi:10.1001/jamaoncol.2015.3709.

eTable 1. Patients who had heart failure or significant asymptomatic LVEF decline eTable 2. Distribution of LVEF and baseline LVEF values by patients’ characteristics eTable 3. Patients who had heart failure or significant asymptomatic LVEF decline eFigure 1. Patients who experienced Grade 3 left ventricular systolic dysfunction eFigure 2. Phase II Study of Paclitaxel + Trastuzumab N = 406.

This supplementary material has been provided by the authors to give readers additional information about their work.

© 2015 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ by a Non-Human Traffic (NHT) User on 06/07/2020

Supplement Table of Contents eTable 1. Patients who had heart failure or significant asymptomatic LVEF decline eTable 2. Distribution of LVEF and baseline LVEF values by patients’ characteristics eTable 3. Patients who had heart failure or significant asymptomatic LVEF decline eFigure. Patients who experienced Grade 3 left ventricular systolic dysfunction



eTable 1. Rules for trastuzumab continuation or hold based on LVEF

changes Relationship of LVEF to LLN

Absolute Decrease of <

10%

Absolute Decrease of 10-

15%

Absolute Decrease of >

16% Within Normal

Limits Continue Continue Hold*

1-5% below LLN Continue* Hold* Hold* >6% below LLN Continue* Hold* Hold*

*Repeat LVEF assessment after 4 weeks -If criteria for continuation met-continue/resume trasstuzumab -If 2 consecutive holds occur-discontinue trastuzumab



eTable 2. Distribution of LVEF and baseline LVEF values by patients’

characteristics

LVEF=left ventricular ejection fraction

LVEF values N=406 % 50-55% 40 10 56-59% 43 10 60-69% 207 51 >70% 116 29



etable 3. Patients who had heart failure or significant asymptomatic LVEF decline

Patient A

ge

CV risk factors

Baseline CV meds

LVEF (BSLN)

LVEF (12 w and after)

LVEF (6 mo and after)

LVEF (after 6 mo and 1 year)

HF specific treatment

Subsequent LVEF and Follow-up symptom status

Symptomatic

#257 67

HL

atorvastatin, aspirin

55%

54%

60%

37% (HF at 11 mo)

lisinopril

60% (at 16 mo) 66% (at 27 mo) asymptomatic

#309 5

6 arrhythmogenic right ventricular dysplasia

metoprolol and propranolol

66%

61% 50%

(HF at 6 mo)

NR (at 1 year)

furosemide, ramipril, and carvedilol

51% (at 7 mo) 54% (at 8 mo) 56% (at 18 mo) Asymptomatic

Asymptomatic (Persistent During Therap



y)

#168

71

HTN, CVA, DM II, HL

amlodipine, atenolol, lovastatin, aspirin/dipyridamole, and metformin

55%

45% (at 12 weeks) and 46% (at 4 mo, off study)

NR NR (at 1 year)

none added

53% (at 5 mo) 45% (at 10 mo) asymptomatic

#325

56

none

none

55%

50%

45% (at 6 mo)

45% (at 7 mo, off study) 35% (at 9 mo) 25% (at 1 year)

lisinopril, losartan, carvedilol

40% (at 21 mo) asymptomatic

# 254 35

none none 60%

45% (at 12 weeks) and 45% (at 4 mo, was not

61% 55% (at 1 year)

none

asymptomatic



withdrawn from study, violation)

Patient Age

CV risk factors

Baseline CV meds

LVEF (BSLN)






Asymptomatic (Non-persistent During Therapy)

# 27

41

none

none

70%

70%

55%

50% (20% drop from BSLN)*

none

asymptomatic

# 50 68

HTN, Hyperlipidemia

fosinopril, hydrochlorothiazide,

simvastatin,

70%

68%

56%

54% (16% drop

none added

asymptomatic



from BSLN)*

# 71

46

none

none

68%

52% (at 12 weeks, 16% drop from BSLN) 60% (at 4 mo; recovered)

66% (at 6 mo) 65% (at 9 mo)

53%

none

65% (at 21 mo asymptomatic

#97

52

none

none

60%

60%

45% (at 6 mo, 15% drop from BSLN and below LLN) 60% (at 7 mo; recovered)

63%

none

asymptomatic

# 147

63

HTN

none

77%

62%

60%

(at 6 mo, 17% drop

60%

none

asymptomatic



but H was not held, violation)

#173 58

HTN

amlodipine besylate and benazepril, hydrochlorothiazide

71%

64%

47% (at 6 mo, 24% drop from BSLN) and 62% (at 7 mo; recovered)

58%

carvedilol added

asymptomatic

Patient Age

CV risk factors

Baseline CV meds

LVEF (BSLN)






Asymptomatic (Non-persistent During Therapy) Continued

#227

41

none

none

68%

58%

63%

51% (17

none

65% (at 25 mo)



% drop from BSLN)

asymptomatic

#279 43

none

none

74

%

66%

60%

56% (18% drop from BSLN)*

lisino

pril

asympt

omatic

#338

59

none

none

75%

72%

60%

58% (17% drop from BSN)*

none

asymptomatic

#360 44

none lisinopril (prophylaxis)#

55%

55% 50% 41% (14% drop from BSLN and below LL

valsartan#

45% (at 33 months) asymptomatic



N) C=cardiovascular, LVSD=left ventricular systolic dysfunction; LVEF=left

ventricular ejection fraction; BSLN=baseline; NR= not reported;

HTN=hypertension, CVA=cerebral vascular accident; DM=diabetes mellitus;

HL=hyperlipidemia; LLN=lower limit of normal; H=trastuzumab

#Lisinopril was started prophylactically due to concerns of cardiotoxicity on

trastuzumab. This was switched to valsartan due to the patient experiencing dry

cough while on lisinopril. Valsartan dose was not escalated with LVEF decline.

*Patients did not have follow-up ECHO or MUGA.



Month 0 3 6 11 16 27

Chemo LVEF

eFigure 1. Patient # 257 who experienced Grade 3 left ventricular systolic dysfunction at 11 months.

Month 0 3 6 7 8 18

Chemo LVEF

eFigure 1. Patient # 309 who experienced Grade 3 left ventricular systolic dysfunction at 6 months.



eFigure 2.


supplementary online content - jama...supplementary online content dang ct, guo h, najita j, et al....

Documents