Cardiac safety of dual anti-HER2 blockade with pertuzumab plus trastuzumab (P+T) in the APHINITY trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 510-510
Author(s):  
Evandro de Azambuja ◽  
Daniel Eiger ◽  
Marion Jennifer Procter ◽  
Noam Falbel Ponde ◽  
Sebastien Guillaume ◽  
...  
Keyword(s):  
Standard Of Care ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Class Iii ◽  
Cardiac Safety ◽  
Cardiac Events ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Dual Blockade

510 Background: Trastuzumab (T) increases the incidence of cardiac events (CEs) in patients (pts) with early breast cancer (BC). Dual blockade with P+T improves BC outcomes and is the standard of care for high-risk HER2-positive BC pts following the phase 3 APHINITY trial that evaluated the addition of P or placebo (Pla) to T and chemotherapy (CT). We analyzed the cardiac safety of P+T in APHINITY. Methods: APHINITY eligibility required a left ventricular ejection fraction (LVEF) ≥55% at study entry. LVEF assessment was performed every 3 months (mos) during treatment, every 6 mos up to month 36, and yearly thereafter. Primary CE was defined as heart failure (HF) class III/IV and a significant decrease in LVEF of at least 10 percentage points from baseline and to <50%, or cardiac death. Secondary CE was defined as a confirmed significant decrease in LVEF or CEs confirmed by the cardiac advisory board. Results: The safety analysis population consists of 4,769 pts. With 74 mos median follow-up (FU), CEs were observed in 159 pts (3.3%): 83 (3.5%) in the P+T and 76 (3.2%) in Pla+T arms, respectively. Most CEs occurred during anti-HER2 therapy: 123/159 (77.4%) and were asymptomatic or mildly symptomatic LVEF decrease (133/159; 83.6%) (Table 1). There were 2 cardiac deaths in each arm (0.1%). More CEs occurred in pts receiving an anthracycline-based CT compared to those receiving non-anthracycline CT (139 vs. 20 CEs, respectively). Acute recovery from a CE based on subsequent LVEF values was observed in 127/155 pts (81.9%). Conclusions: Dual blockade with P+T does not increase the risk of CE compared to Pla+T alone. The use of anthracycline-based CT increases the risk of a CE; hence non-anthracycline CT may be considered particularly in pts with other cardiovascular risk factors. Clinical trial information: NCT01358877. [Table: see text]

Neoadjuvant treatment of HER2 positive breast cancer with concomitant nonpegylated liposomal doxorubicin (NPLD), docetaxel and dual blockade with trastuzumab and pertuzumab: A retrospective analysis of pCR and cardiac safety.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12061-e12061
Author(s):  
Daniel Egle ◽  
Christine Brunner ◽  
Theresa Czech ◽  
Thomas Jaeger ◽  
Alois Lang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Treatment ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cardiac Safety ◽  
Her2 Positive ◽  
Standard Dosage ◽  
Ventricular Ejection Fraction ◽  
Safety And Efficacy ◽  
Dual Blockade

e12061 Background: Neoadjuvant treatment in HER2 overexpressing early breast cancer (EBC) has increased considerably. The Neosphere study, in which dual blockade of HER2 was combined with docetaxel resulted in favorable pCR rates. The addition of anthracyclines could play an important role in enhancing the effectiveness. The use of NPLD might be valuable in combination with HER2 targeted therapies. Safety and efficacy of NPLD, taxotere and trastuzumab was reported in the ABSCG 32 study. There is only little data about the cardiac safety and efficacy in combination with dual HER2 blockade. We report pCR-rate and cardiac safety of a single arm, retrospective, multicenter analysis of neoadj. treatment for HER2+ EBC. Methods: In this study 98 women with HER2+ EBC were investigated in 4 oncological departments in Austria. All patients were treated with NPLD (50 mg/m²), docetaxel (75 mg/m²) concurrent with trastuzumab and pertuzumab in standard dosage for 6 cycles as neoadjuvant therapy. All patients were free of cardiovascular disease and had a left ventricular ejection fraction (LVEF) of ≥50%. Cardiac function was measured by LVEF. All patients underwent surgery after neoadjuvant chemotherapy. The absence of any residual invasive cancer in the breast and axilla was defined as pathological complete response (pCR). Median follow up was 1.7 years. Results: Median age was 49 years. pCR rate was 73%. In this cohort a negative estrogen-and progesteron receptor was predictive for pCR (p<0.001). These patients achieved pCR in 89%. No patient progressed during treatment. Only one patient(1%) suffered symptomatic heart failure after surgery. Conclusions: We observed a considerably high rate of pCR in HER2-positive EBC treated with a combination of NPLD, docetaxel, trastuzumab and pertuzumab. Hormone receptor negativity was highly predictive for pCR. The addition of NPLD entails a very favorable cardiotoxicity profile. This regimen is a safe and highly effective treatment option in patients with HER-2 positive EBC.

Trastuzumab-Associated Cardiac Events at 8 Years of Median Follow-Up in the Herceptin Adjuvant Trial (BIG 1-01)

2014 ◽  
Vol 32 (20) ◽  
pp. 2159-2165 ◽  
Author(s):  
Evandro de Azambuja ◽  
Marion J. Procter ◽  
Dirk J. van Veldhuisen ◽  
Dominique Agbor-Tarh ◽  
Otto Metzger-Filho ◽  
...  
Keyword(s):  
Early Stage ◽  
Growth Factor Receptor ◽  
Severe Congestive Heart Failure ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cardiac Events ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Low Incidence

Purpose To document the rate and outcome of trastuzumab-associated cardiac dysfunction in patients following 1 or 2 years of adjuvant therapy. Patients and Methods The Herceptin Adjuvant (HERA) trial is a three-arm, randomized trial comparing 2 years or 1 year of trastuzumab with observation in 5,102 patients with human epidermal growth factor receptor 2 (HER2) –positive early-stage breast cancer. Cardiac function was closely monitored. Eligible patients had left ventricular ejection fraction (LVEF) ≥ 55% at study entry following neoadjuvant chemotherapy with or without radiotherapy. This 8-year median follow-up analysis considered patients randomly assigned to 2 years or 1 year of trastuzumab or observation. Results The as-treated safety population for 2 years of trastuzumab (n = 1,673), 1 year of trastuzumab (n = 1,682), and observation (n = 1,744) is reported. Cardiac adverse events leading to discontinuation of trastuzumab occurred in 9.4% of patients in the 2-year arm and 5.2% of patients in the 1-year arm. Cardiac death, severe congestive heart failure (CHF), and confirmed significant LVEF decrease remained low in all three arms. The incidence of severe CHF (0.8%, 0.8%, and 0.0%, respectively) and confirmed significant LVEF decrease (7.2%, 4.1%, and 0.9%, respectively) was significantly higher in the 2-year and 1-year trastuzumab arms compared with the observation arm. Severe CHF was the same for 2-year and 1-year trastuzumab. Of patients with confirmed LVEF decrease receiving 2-year trastuzumab, 87.5% reached acute recovery. Of patients with confirmed LVEF decrease receiving 1-year trastuzumab, 81.2% reached acute recovery. Conclusion Long-term assessment at 8-year median follow-up confirms the low incidence of cardiac events for trastuzumab given sequentially after chemotherapy and radiotherapy, and cardiac events were reversible in the vast majority of patients.

scholarly journals Incidence of Cardiotoxicity and Validation of the Heart Failure Association- International Cardio-Oncology Society risk stratification Tool in Patients Treated with Trastuzumab for HER2-Positive Early Breast Cancer.

2021 ◽  
Author(s):  
Nicolò Matteo Luca Battisti ◽  
Maria Sol Andres ◽  
Karla A Lee ◽  
Tharshini Ramalingam ◽  
Tamsin Nash ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Heart Failure ◽  
Early Breast Cancer ◽  
Nyha Class ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Class Iii ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Very High

Abstract PurposeTrastuzumab improves survival in patients with HER2+ early breast cancer. However, cardiotoxicity remains a concern, particularly in the curative setting, and there are limited data on its incidence outside of clinical trials. We retrospectively evaluated the cardiotoxicity rates (left ventricular ejection fraction [LVEF] decline, congestive heart failure [CHF], cardiac death or trastuzumab discontinuation) and assessed the performance of a proposed model to predict cardiotoxicity in routine clinical practice.MethodsPatients receiving curative trastuzumab between 2011-2018 were identified. Demographics, treatments, assessments and toxicities were recorded. Fisher’s exact test, chi-squared and logistic regression were used.Results931 patients were included in the analysis. Median age was 54 years (range 24-83) and Charlson comorbidity index 0 (0-6), with 195 patients (20.9%) aged 65 or older. 228 (24.5%) were smokers. Anthracyclines were given in 608 (65.3%). Median number of trastuzumab doses was 18 (1-18). The HFA-ICOS cardiovascular risk was low in 401 patients (43.1%), medium in 454 (48.8%), high in 70 (7.5%) and very high in 6 (0.6%).Overall, 155 (16.6%) patients experienced cardiotoxicity: LVEF decline≥10% in 141 (15.1%), falling below 50% in 55 (5.9%), CHF NYHA class II in 42 (4.5%) and class III-IV in 5 (0.5%) and discontinuation due to cardiac reasons in 35 (3.8%). No deaths were observed.Cardiotoxicity rates increased with HFA-ICOS score (14.0% low, 16.7% medium, 30.3% high/very high; p=0.002). ConclusionsCardiotoxicity was relatively common (16.6%), but symptomatic heart failure on trastuzumab was rare in our cohort. The HFA-ICOS score identifies patients at high risk of cardiotoxicity

Predicting mortality for patients with heart failure beyond oxygen consumption: a prognostic risk score

2021 ◽  
Author(s):  
Hanaa Shafiek ◽  
Andres Grau ◽  
Jaume Pons ◽  
Pere Pericas ◽  
Xavier Rossello ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Risk Score ◽  
Cardiac Transplantation ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Functional Evaluation ◽  
Cardiac Events ◽  
Ventricular Ejection Fraction

Background: Cardiopulmonary exercise test (CPET) is a crucial tool for the functional evaluation of cardiac patients. We hypothesized that VO2 max and VE/VCO2 slope are not the only parameters of CPET able to predict major cardiac events (mortality or cardiac transplantation urgently or elective). Objectives: We aimed to identify the best CPET predictors of major cardiac events in patients with severe chronic heart failure and to propose an integrated score that could be applied for their prognostic evaluation. Methods: We evaluated 140 patients with chronic heart failure who underwent CPET between 2011 and 2019. Major cardiac events were evaluated during follow-up. Univariate and multivariate logistic regression analysis were applied to study the predictive value of different clinical, echocardiographic and CPET parameters in relation to the major cardiac events. A score was generated and c-statistic was used for the comparisons. Results: Thirty-nine patients (27.9%) died or underwent cardiac transplantation over a median follow-up of 48 months. Five parameters (maximal workload, breathing reserve, left ventricular ejection fraction, diastolic dysfunction and non-idiopathic cardiomyopathy) were used to generate a risk score that had better risk discrimination than NYHA dyspnea scale, VO2 max, VE/VCO2 slope > 35 alone, and combined VO2 max and VE/VCO2 slope (p= 0.009, 0.004, < 0.001 and 0.005 respectively) in predicting major cardiac events. Conclusions: A composite score of CPET and clinical/echocardiographic data is more reliable than the single use of VO2max or combined with VE/VCO2 slope to predict major cardiac events.

The Safety of Dose-Dense Doxorubicin and Cyclophosphamide Followed by Paclitaxel With Trastuzumab in HER-2/neuOverexpressed/Amplified Breast Cancer

2008 ◽  
Vol 26 (8) ◽  
pp. 1216-1222 ◽  
Author(s):  
Chau Dang ◽  
Monica Fornier ◽  
Steven Sugarman ◽  
Tiffany Troso-Sandoval ◽  
Diana Lake ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cardiac Safety ◽  
Cardiac Events ◽  
Ventricular Ejection Fraction ◽  
Time To Recurrence ◽  
Her 2 ◽  
Dose Dense

PurposeDose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (P) is superior to every 3-weekly AC followed by P. Given the demonstrated cardiac safety for trastuzuamb (T) with conventionally scheduled AC followed by P, we tested the safety of dd AC followed by P with T. The primary end point was cardiac safety, and the secondary end points were time to recurrence and overall survival.MethodsPatients with HER-2/neu immunohistochemistry (IHC) 3+ or fluorescent in situ hybridization (FISH)-amplified breast cancer and baseline left ventricular ejection fraction (LVEF) of ≥ 55% were enrolled, regardless of tumor size or nodal status. Treatment consisted of AC (60/600 mg/m2) × 4 followed by P (175 mg/m2) × 4 every 2-weekly with pegfilgrastim (6 mg on day 2) + T ×1 year. LVEF by radionuclide scan was obtained at baseline, at months 2, 6, 9, and 18.ResultsFrom January 2005 to November 2005, 70 patients were enrolled. The median age was 49 years (range, 27 to 72 years); median LVEF at baseline was 68% (range, 55% to 81%). At month 2 in 70 of 70 patients, the median LVEF was 67% (range, 58% to 79%); at month 6 in 67 of 70 patients, it was 66% (range, 52% to 75%); at month 9 in 68 of 70 patients, it was 65% (range, 50% to 75%); and at month 18 in 48 of 70 patients, it was 66% (range, 57% to 75%). As of December 1, 2007, the median follow-up was 28 months (range, 25 to 35 months). One patient (1%) experienced conestive heart failure (CHF). There were no cardiac deaths.ConclusionDose-dense AC followed by P/T followed by T is feasible and is not likely to increase the incidence of cardiac events compared to established regimens.

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

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1106-1106 ◽  
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.

Fluorouracil, Epirubicin, and Cyclophosphamide With Either Docetaxel or Vinorelbine, With or Without Trastuzumab, As Adjuvant Treatments of Breast Cancer: Final Results of the FinHer Trial

2009 ◽  
Vol 27 (34) ◽  
pp. 5685-5692 ◽  
Author(s):  
Heikki Joensuu ◽  
Petri Bono ◽  
Vesa Kataja ◽  
Tuomo Alanko ◽  
Riitta Kokko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Treatment ◽  
Disease Free Survival ◽  
Left Ventricular ◽  
Axillary Node ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Ventricular Ejection Fraction

Purpose Docetaxel has not been compared with vinorelbine as adjuvant treatment of early breast cancer. Efficacy and long-term safety of a short course of adjuvant trastuzumab administered concomitantly with chemotherapy for human epidermal growth factor receptor 2 (HER2) –positive cancer are unknown. Patients and Methods One thousand ten women with axillary node–positive or high-risk node-negative breast cancer were randomly assigned to receive three cycles of docetaxel or vinorelbine, followed in both groups by three cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC). Women with HER2-positive cancer (n = 232) were further assigned to either receive or not receive trastuzumab for 9 weeks with docetaxel or vinorelbine. The median follow-up time was 62 months after random assignment. Results Women assigned to docetaxel had better distant disease–free survival (DDFS) than those assigned to vinorelbine (hazard ratio [HR] = 0.66; 95% CI, 0.49 to 0.91; P = .010). In the subgroup of HER2-positive disease, patients treated with trastuzumab tended to have better DDFS than those treated with chemotherapy only (HR = 0.65; 95% CI, 0.38 to 1.12; P = .12; with adjustment for presence of axillary nodal metastases, HR = 0.57; P = .047). In exploratory analyses, docetaxel, trastuzumab, and FEC improved DDFS compared with docetaxel plus FEC (HR = 0.32; P = .029) and vinorelbine, trastuzumab, and FEC (HR = 0.31; P = .020). The median left ventricular ejection fraction of trastuzumab-treated patients remained unaltered during the 5-year follow-up; only one woman treated with trastuzumab was diagnosed with a heart failure. Conclusion Adjuvant treatment with docetaxel improves DDFS compared with vinorelbine. A brief course of trastuzumab administered concomitantly with docetaxel is safe and effective and warrants further evaluation.

scholarly journals 85 Diuretics trajectories in dilated cardiomyopathy

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Vincenzo Nuzzi ◽  
Antonio Cannatà ◽  
Paolo Manca ◽  
Caterina Gregorio ◽  
Giulia Barbati ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Nyha Class ◽  
Diuretic Therapy ◽  
Left Ventricular ◽  
Equivalent Dose ◽  
Left Ventricular Ejection ◽  
Class Iii ◽  
Ventricular Ejection Fraction ◽  
Kaplan Meier

Abstract Aims Diuretics in heart failure (HF) are commended to relieve symptoms at lowest dosage effective. Dilated cardiomyopathy (DCM) is a particular HF setting with several variables that may influence disease trajectory. We aimed to assess the long-term use of diuretics in DCM, the possibility of withdrawal and to explore the prognostic correlations. Methods and results All consecutive DCM patients enrolled from 1990 to 2018 were considered eligible. All the patients had available the information about the furosemide-equivalent dose at baseline and at follow-up evaluation within 24 months. Patients were categorized in stable (diuretic dose variation &lt;50%), increasers (diuretics dose increase ≥50% or initiation of diuretic therapy), and decreasers (diuretics dose decrease ≥50% or never prescribed diuretics in the 24-months observation period). The prognostic role of the diuretics trajectory group was assessed with Kaplan Meier analysis and with a time-dependent multivariable model. The outcome measure was a composite of all-cause death/heart transplantation/HF hospitalization (ACD/HTx/HFH). 908 patients were included [mean age 50 ± 16, 70% male sex, 24% NYHA class III or IV, mean left ventricular ejection fraction (LVEF) 31 ± 9%, 66% treated with diuretics at baseline]. The furosemide-equivalent dose at enrolment had a linear association with the risk of outcome. Compared to other groups, decreaser patients were younger, had less HF symptoms, higher LVEF and more dilated left atrium. Decreasers had a lower prescription rate of diuretics and less frequent indication to renin-angiotensin inhibitors and mineralocorticoid receptors antagonists. Over a median follow-up of 122 (62–195) months decreasers had the lowest incidence of outcome, followed by stable, while increasers had the worst outcome (P &lt; 0.001). After adjustment for other prognosticators, compared to stable patients, decreasers had a reduced risk of ACD/HTx/HFH [HR: 0.497 (95% CI: 0.337–0.731)] while increasers had the highest risk of adverse outcome [HR: 2.027 (95% CI: 1.254–3.276)]. Similarly, amongst patients taking diuretics at baseline, the diuretics withdrawal was in independent outcome predictor. The only multivariable predictors of diuretics withdrawal were younger age and lower furosemide-equivalent dose at enrolment. Conclusions In DCM patients the diuretics dose at baseline is a strong prognosticator. Diuretics dose reduction or its withdrawal provides a prognostic benefit on hard outcome. Diuretics tapering in selected patients should be considered in the short-term follow-up to improve DCM prognosis.

A report of cardiac events in a phase II clinical study using trastuzumab combined with pertuzumab in HER2-positive metastatic breast cancer (MBC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1028-1028
Author(s):  
C. C. Portera ◽  
J. M. Walshe ◽  
N. Denduluri ◽  
A. W. Berman ◽  
U. Vatas ◽  
...  
Keyword(s):  
Chest Wall ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Erbb Receptors ◽  
Cardiac Events ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction

1028 Background: T and P are humanized recombinant monoclonal antibodies (MoAB) that target different epitopes of HER2 extracellular domain. P blocks HER2’s ability to heterodimerize with other HER/ErbB receptors. Methods: This Ph II trial evaluates the efficacy and safety of T with P in patients (pts) with HER2+ (FISH +) MBC who had progressive disease (PD) on T-based therapy. Eligible pts must have had = 3 T-based regimens, normal (nl) left ventricular ejection fraction (EF=55%) and without significant cardiac history. Pts received IV T (6mg/kg) and P (420 mg) every 3 weeks (wks). EKG plus echocardiogram (ECHO) or cardiac MRI and tumor response were assessed every 3 and 6 wks, respectively. Results: Eleven pts received 39 (1 to 13) cycles, 1 pt achieved a partial response (PR) and 3 pts had stable disease. A total of 68 ECHOs and 8 cardiac MRIs were performed. Left ventricular systolic dysfunction (LVSD) with nl EKG was seen in 5 pts; Grade (Gr) 1 (n = 2) (EF 50–55%), Gr 2 (n = 2) (EF 40–50%) and Gr 3 (n = 1) (EF20–40%). Gr 2–3 events were associated with global hypokinesis. Gr 3 event was associated with symptomatic CHF. All 5 pts had received 240mg/m2 cumulative dose of doxorubicin, 2 pts (Gr 2–3) received chest wall radiation, and 1 pt (Gr 1) had HTN. Two pts with Gr 1–2 LVSD had a history of reduced EF during prior T-based treatment, which reversed to nl upon stopping T. Reduced EF appeared within 1–2 cycles, which returned to nl in 3 pts within 1wk to 3 months (mo) post discontinuing T/P. One pt had persistent Gr 2 LVSD 3 mo after the initial event. The pt with Gr 3 LVSD had extensive chest wall disease and died of PD and possibly CHF 2 mo after treatment termination. Conclusions: We observed Gr 1–3 LVSD in patients with HER2+ MBC who received dual MoAB treatment directed at HER2, in which very strict cardiac surveillance guidelines were required. One of 11 pts achieved PR and 1 pt had symptomatic CHF thus far. It is unknown whether the other events would have become symptomatic if treatment had continued. Further evaluation of the efficacy of combination T with P is required to define the overall risk and benefit. No significant financial relationships to disclose.

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