Long-Term Cardiac Tolerability of Trastuzumab in Metastatic Breast Cancer: The M.D. Anderson Cancer Center Experience

PurposeTo evaluate the cardiac safety of long-term trastuzumab therapy in patients with human epidermal growth receptor 2 (HER2) –overexpressing metastatic breast cancer (MBC) treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX).Patients and MethodsAmong 218 MBC patients treated with trastuzumab-based therapy for at least 1 year, 173 patients were assessable for cardiac toxicity. Cardiac events (CEs) were defined as follows: asymptomatic decrease of left ventricular ejection fraction (LVEF) below 50%; decrease of 20 percentage points in LVEF compared with the baseline; or signs or symptoms of congestive heart failure (CHF).ResultsThe median cumulative time for trastuzumab administration was 21.3 months. The median follow-up was 32.6 months (range, 11.8 to 79.0 months). Forty-nine patients (28%) experienced a CE: three patients (1.7%) had an asymptomatic decrease in the LVEF of 20 percentage points, 27 patients (15.6%) experienced grade 2 cardiac toxicity, and 19 patients (10.9%) experienced grade 3 cardiac toxicity. All but three patients had improved LVEF or symptoms of CHF with trastuzumab discontinuation and appropriate therapy. There was one cardiac-related death (0.5%). Baseline LVEF was significantly associated with CE (hazard ratio, 0.94; P = .001). The hazard of a CE among patients taking concomitant taxanes was higher early in the follow-up period but declined during the course of follow-up.ConclusionThe risk of cardiac toxicity of long-term trastuzumab-based therapy is acceptable in this population, and this toxicity is reversible in the majority of the patients. In patients who have experienced a CE, additional treatment with trastuzumab can be considered after recovery of cardiac function.

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Long term cardiac tolerability of trastuzumab in HER-2-overexpressing metastatic breast cancer (MBC)

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.629 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 629-629

Author(s):

V. Guarneri ◽

D. J. Lenihan ◽

V. Valero ◽

J. Durand ◽

K. Broglio ◽

...

Keyword(s):

Cardiac Toxicity ◽

Metastatic Breast ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Percentage Points ◽

Increased Risk ◽

One Year ◽

Experienced Grade

629 Background: The use of trastuzumab is associated with an increased risk of cardiotoxic events such as congestive hearth failure (CHF) and decline in the left ventricular ejection fraction (LVEF). Our objectives were to evaluate the incidence of cardiac dysfunction, to identify risk factors and to evaluate the outcome of patients with MBC treated with trastuzumab for one year or longer. Methods: Among 218 MBC patients treated with trastuzumab-based therapy for at least one year, 173 patients were evaluable for cardiac toxicity. Cardiac events (CE) were defined as follows: 1) asymptomatic drop of LVEF below 50%; 2) drop of 20 percentage points in LVEF compared to the baseline; 3) signs or symptoms of CHF. The cardiac toxicity was graded according the NCI-CTCAE, version 3.0. Results: Median age at the start of trastuzumab therapy was 50 years (range, 26–79), median cumulative time on trastuzumab was 21.3 months (range, 11.6–77.6), and median follow-up was 32.2 months (range, 9.7–79.0). Eighty-five percent of patients received prior anthracyclines (median cumulative doxorubicin dose: 300 mg/m2). Forty-nine patients (28%) experienced a CE: 3 patients (1.7%) had an asymptomatic drop in the LVEF of 20 percentage points; 27 patients (15.6%) experienced grade 2 cardiac toxicity; and 18 patients (10.4%) experienced grade 3 cardiac toxicity. There was one cardiac related death (0.5%). Cardiac event-free survival was 87.3% at 1 year. All but four patients had improved LVEF or symptoms of CHF after stopping trastuzumab or with appropriate therapy. After complete recovery, 26 patients were re treated with trastuzumab; 16 patients did not experience further CE. Concomitant taxane use was the only factor significantly associated with a CE (HR: 4.37, 95%CI 1.06–17.98, p:0.04).Prior anthracycline exposure was not associated with increased risk of CE. Conclusions: The risk of cardiac toxicity of long-term trastuzumab-based therapy is acceptable in this population, and this toxicity is reversible in the majority of the patients. In patients who have experienced a CE, additional treatment with trastuzumab can be considered after recovery of cardiac function. The increased risk of cardiotoxicity associated with taxane administration needs to be further investigated. No significant financial relationships to disclose.

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Post-surgical depressive symptoms and long-term survival in non-metastatic breast cancer patients at 11-year follow-up

General Hospital Psychiatry ◽

10.1016/j.genhosppsych.2016.10.002 ◽

2017 ◽

Vol 44 ◽

pp. 16-21 ◽

Cited By ~ 16

Author(s):

Michael H. Antoni ◽

Jamie M. Jacobs ◽

Laura C. Bouchard ◽

Suzanne C. Lechner ◽

Devika R. Jutagir ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Depressive Symptoms ◽

Cancer Patients ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Term Survival ◽

Long Term Survival

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Abstract P6-16-06: Maintenance immunotherapy in estrogen receptor negative (ER-) locally advanced (LA) and/or metastatic breast cancer (MBC). Long-term follow-up of a phase II study

10.1158/1538-7445.sabcs16-p6-16-06 ◽

2017 ◽

Author(s):

F Recchia ◽

G Candeloro ◽

S Rea

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Metastatic Breast Cancer ◽

Phase Ii Study ◽

Locally Advanced ◽

Metastatic Breast ◽

Long Term Follow Up ◽

Estrogen Receptor Negative

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Phase II Trial of Liposome-Encapsulated Doxorubicin, Cyclophosphamide, and Fluorouracil as First-Line Therapy in Patients With Metastatic Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.1999.17.5.1425 ◽

1999 ◽

Vol 17 (5) ◽

pp. 1425-1425 ◽

Cited By ~ 57

Author(s):

Vicente Valero ◽

Aman U. Buzdar ◽

Richard L. Theriault ◽

Nozar Azarnia ◽

Gustavo A. Fonseca ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Phase Ii ◽

Cardiac Toxicity ◽

Metastatic Breast ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Survival Duration ◽

First Line ◽

Ventricular Ejection Fraction

PURPOSE: To determine the efficacy and safety profile, including the risk for cardiac toxicity, of liposome-encapsulated doxorubicin (TLC D-99), fluorouracil (5-FU), and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-one women were registered in this phase II study. All patients had measurable disease and no previous chemotherapy for MBC. Treatment consisted of TLC D-99 60 mg/m2 and cyclophosphamide 500 mg/m2 on day 1 and 5-FU 500 mg/m2 on days 1 and 8 every 3 weeks. Serial cardiac monitoring, including endomyocardial biopsies, was performed. RESULTS: The overall response rate was 73% (95% confidence interval, 57% to 86%). The median duration of response was 11.2 months, the median time to treatment failure was 8.1 months, and the median overall survival duration was 19.4 months. The median number of cycles per patient was 10. The median cumulative dose of TLC D-99 was 528 mg/m2. Ten patients required hospitalization for febrile neutropenia. Nausea/vomiting, stomatitis, and fatigue higher than grade 2 occurred in 12%, 15%, and 41% of patients, respectively. Twenty-one patients reached a cumulative doxorubicin dose greater than 500 mg/m2. Three patients (7%) were withdrawn from the study due to protocol-defined cardiac toxicity, two because of a decrease in left ventricular ejection fraction to ≤ 40%, and one because her endomyocardial biopsy result was grade 1.5. One patient had congestive heart failure that was probably nonanthracycline related. CONCLUSION: This chemotherapy regimen, including TLC D-99, was highly active against MBC and associated with low cardiac toxicity despite high cumulative doses of doxorubicin.

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Cardiac safety of pegylated liposomal doxorubicin (PLD) in combination with trastuzumab (T) in patients with metastatic breast cancer (MBC): Results from a multicenter phase II study

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.1106 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 1106-1106 ◽

Cited By ~ 1

Author(s):

E. Stickeler ◽

D. O. Watermann ◽

J. Woll ◽

M. Foeldi ◽

G. Gitsch

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Phase Ii ◽

Metastatic Breast ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Cardiac Safety ◽

Ventricular Ejection Fraction ◽

Cardiac Side Effects

1106 Background: Combination therapy of doxorubicin and trastuzumab is highly effective for Her2 positive MBC but characterized by frequent cardiac toxicity (CT). PLD can significantly reduce CT compared to conventional doxorubicin. Patients and Methods: 15 patients were enrolled in a phase II trial to evaluate cardiac safety of T (4 mg/Kg loading dose day 2, followed by weekly 2 mg/Kg) in combination with PLD (40 mg/m2 IV bolus day 1, q 28 d). 75% of pts. presented with more than 1 metastatic site and 40% for second line treatment. PLD was administered for 6 or 9 cycles, respectively, T until disease progression. To assess CT, all pts were evaluated with electrocardiogram (ECG) and echocardiograms (E) for Left Ventricular Ejection Fraction (LVEF) at baseline, every cycle during PLD and T, and every three months during T therapy alone. CT was defined as appearance of signs/ symptoms of congestive heart failure and/or an absolute decrease in LVEF > 10 units (below 50%) or decrease in LVEF > 15 units (above 50%). Results: Four pts. received 6 cycles, 4 pts. received 9 cycles of PLD, 4 pts discontinued treatment due to PD, 3 pts. due to toxicity. After a median follow up time of 15.4 months, 6 pts. (42.9%) demonstrated a clinical benefit and median OS was 16.2 months. Non cardiac side effects were mild with only 3 CTC Grade 3 events of 247 treatment cycles (1.2%). Three pts. developed minor ECG changes without pathological significance and 5 pts. had minor changes in their E with slight diastolic (n=3) or systolic (n=2) dysfunction. During follow-up, 3 pts. were diagnosed with pathological E findings, including 1 slight decrease of LVEF, one diffuse hypokinesia and one strong decrease in LVEF.The median LVEF in the study cohort was 66.1% at baseline, 62.7% after 6 cycles of therapy, 64.4% at the first follow up and did not change significantly until the 5 th examination. Conclusions: This study supports the combination of PLD and H in pts. with HER2 overexpressing metastatic breast cancer as a safe and feasible therapy. Due to the promising clinical response rates in this prognostically unfavorable group, this combination should be evaluated in larger studies as a potential regimen for adjuvant treatment of breast cancer. No significant financial relationships to disclose.

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