Tolerability and cardiac safety of neo/adjuvant trastuzumab-based chemotherapy regimens for HER2+ breast cancer: A single institution experience.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11508-e11508
Author(s):  
Potjana Jitawatanarat ◽  
Ellen Kossoff ◽  
Grazyna Riebandt ◽  
Ellis Glenn Levine ◽  
Tracey L. O'Connor ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Cardiac Safety ◽  
Cardiac Events ◽  
Adjuvant Trastuzumab ◽  
Her2 Breast Cancer ◽  
Comorbidity Index ◽  
Grade 3 ◽  
Selection Of Patients ◽  
Selection Of

e11508 Background: Docetaxel/carboplatin/trastuzumab (H) (TCaH) and doxorubicin/cyclophosphamide/paclitaxel/H (AC-TH) and its variants are recommended by standard guidelines for neoadjuvant and adjuvant treatments for HER2+ breast cancer. Docetaxel/cyclophosphamide/H (TCyH) has also been used in clinical practice. Tolerability and cardiac safety among these regimens have not been well described. Methods: We retrospectively reviewed HER2+ early stage breast cancer who received neo/adjuvant H at RPCI between 2004-2011. Acute toxicities of different regimens (AC-TH and its variants, TCaH, TCyH) were evaluated. Cardiac events were defined as symptomatic congestive heart failure (CHF) and/or asymptomatic decline of ejection fraction (EF) that resulted in holding H. Results: 177 patients were identified (AC-TH=114, TCaH=39, TCyH=24). Patients who received AC-TH were younger, had less comorbidity, including cardiac history, and received less GCSF support. AC-TH regimens were associated with more febrile neutropenia (FN), grade 3-4 neutropenia, and dose delay (Table). Overall cardiac events were observed in 18% (anthracyclines 14% vs non-anthracyclines 9%; p=0.346). Termination of H was not significantly different between patients treated with anthracyclines (4%) vs non-anthracyclines (2%), nor was the CHF rate (4% vs 6%). Median absolute EF decline was also similar (5% vs 4%). After adjustment for age ≥65, cardiac history, baseline EF <55%, and Charlson Comorbidity Index, patients treated with anthracyclines showed a trend toward increased cardiac events (OR 4.53, 95% CI 0.99-20.5; p=0.05) in multivariate analysis. Conclusions: Although physician selection of patients for trastuzumab directed therapy lessens overall toxicity, the acute toxicity and cardiac event rate among those considered the most fit remains considerable when an anthracycline is introduced. [Table: see text]

Adjuvant radiotherapy (RT) and trastuzumab in stage I-IIA breast cancer: Toxicity data from North Central Cancer Treatment Group Phase III trial N9831

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 523-523 ◽  
Author(s):  
M. Y. Halyard ◽  
T. M. Pisansky ◽  
L. J. Solin ◽  
L. B. Marks ◽  
L. J. Pierce ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Cardiac Events ◽  
Concurrent Administration ◽  
Adjuvant Trastuzumab ◽  
Her2 Breast Cancer ◽  
Significant Difference

523 Background: Adjuvant trastuzumab (Herceptin [H]) with chemotherapy improves outcome in HER2+ breast cancer (BC). Preclinical studies suggest H may enhance RT. We herein assess if H given with adjuvant RT increases adverse events (AE) after breast conserving surgery or mastectomy. Methods: N9831 randomized 3505 women with pT1–3N1–2M0, pT2–3N0M0, or pT1cN0M0 (ER/PR negative) HER2+ BC to doxorubicin (A) and cyclophosphamide (C) followed by weekly paclitaxel (T), AC→T→H, or AC→TH→H. Post-lumpectomy breast ± nodal RT was recommended, as was post-mastectomy chest wall + nodal RT (>3 nodes +); internal mammary RT was prohibited. RT started within 5 weeks of completion of T and allowed concurrently with H. 2324 eligible patients were enrolled on study prior to April 25, 2004: 1460 patients receiving RT are available for analysis of RT-associated AEs. Also, 1286 patients on +H arms who completed T (908 +RT and 378 -RT) are available for analysis of clinical cardiac events (CE). Rates of RT-associated AEs were compared across treatment arms, and rates of CE were compared for +RT vs -RT patients within +H arms. All reported p-values are for chi-squared statistics. Results: With a median follow-up of 1.5 years, significant differences among arms in RT-associated AEs were not identified. No significant differences across arms in +RT patients existed in the incidence of skin reaction (p=0.78), pneumonitis (p=0.78), dyspnea (p=0.87), cough (p=0.54), esophageal dysphagia (p=0.26), or neutropenia (p=0.16). There was a significant difference in +RT patients in the incidence of leukopenia (p=0.02) with higher incidence rates in the arms receiving H. RT did not increase the frequency of CE. In the AC→T→H arm, the incidence of CE was 2.2% in +RT patients versus 2.9% in -RT patients. In the AC→TH→H arm, the incidence of CE was 1.5% in +RT patients versus 6.3% in -RT patients. No difference in CE was seen between left- and right-sided RT fields in +RT patients in either +H arm. Conclusion: Concurrent administration of adjuvant RT with H in early stage breast cancer patients is not associated with an increased incidence of acute RT AEs. Further follow-up is required to assess late AEs. No significant financial relationships to disclose.

Cardiac safety in a phase II study of trastuzumab emtansine (T-DM1) following anthracycline-based chemotherapy as adjuvant or neoadjuvant therapy for early-stage HER2-positive breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 532-532 ◽  
Author(s):  
Chau T. Dang ◽  
Luca Gianni ◽  
Gilles Romieu ◽  
Luc Dirix ◽  
Mario Campone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Early Stage ◽  
Left Ventricular ◽  
Cardiac Safety ◽  
Cardiac Events ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Grade 3 ◽  
Positive Breast Cancer

532 Background: T-DM1 has demonstrated clinical activity as a single agent in patients (pts) with previously untreated MBC. In a previous phase II randomized trial of T-DM1 vs trastuzumab + docetaxel, T-DM1 had no clinically significant cardiac events, no cases of post-baseline left ventricular ejection fraction (LVEF) ≤40%, and fewer grade ≥3 adverse events (AEs; Hurvitz, ESMO 2011). This phase II study assessed the clinical safety and feasibility of T-DM1 following anthracycline-based chemotherapy in the adjuvant or neoadjuvant setting for early-stage HER2-positive breast cancer. Methods: TDM4874g (NCT01196052) is a phase II single-arm, open-label study of T-DM1 (3.6 mg/kg q3w IV; up to 17 cycles) following completion of doxorubicin/cyclophosphamide (AC; q2w or q3w for 4 cycles), or 5-fluorouracil/epirubicin (100 mg/m2)/cyclophosphamide (FEC; q3w for 3-4 cycles) chemotherapy in pts with early-stage HER2-positive breast cancer. Pre-chemotherapy LVEF by MUGA/ECHO ≥55% was required for enrollment. Co-primary endpoints are safety and rate of pre-specified cardiac events following initiation of T-DM1 treatment. An interim analysis was planned for the first 60 pts evaluable for cardiac safety (received ≥1 T-DM1 dose). Results: For pts in the interim analysis (20 received AC, 40 FEC), the most common all-grade T-DM1-related AEs were nausea (n=20), asthenia (n=17), and headache (n=17); 8 pts had grade 3/4 T-DM1-related AEs (including 3 with grade 3 increased aspartate aminotransferase [AST] and/or alanine aminotransferase [ALT]). No deaths occurred. Two pts had AEs leading to T-DM1 discontinuation (grade 3 AST and grade 2 ALT increase; grade 3 thrombocytopenia). No pre-specified cardiac events occurred; no pts delayed or discontinued T-DM1 due to cardiac AEs; there were no reports of grade ≥2 left ventricular systolic dysfunction, heart failure, or LVEF <50%. Results will be updated with data from all 153 enrolled pts. Conclusions: T-DM1 following anthracycline-based chemotherapy was not associated with cardiac toxicity in pts with early-stage HER2-positive breast cancer; this study continues without modification.

Effect of PTEN protein expression on benefit to adjuvant trastuzumab in early-stage HER2+ breast cancer in NCCTG adjuvant trial N9831.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 10504-10504 ◽  
Author(s):  
E. A. Perez ◽  
A. C. Dueck ◽  
M. M. Reinholz ◽  
B. Chen ◽  
X. Geiger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Early Stage ◽  
Adjuvant Trastuzumab ◽  
Pten Protein ◽  
Adjuvant Trial ◽  
Her2 Breast Cancer

scholarly journals Duration and Toxicity of Adjuvant Trastuzumab in Older Patients With Early-Stage Breast Cancer: A Population-Based Study

2014 ◽  
Vol 32 (9) ◽  
pp. 927-934 ◽  
Author(s):  
Ines Vaz-Luis ◽  
Nancy L. Keating ◽  
Nancy U. Lin ◽  
Huichuan Lii ◽  
Eric P. Winer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Older Women ◽  
Older Patients ◽  
Early Stage ◽  
Treatment Completion ◽  
Early Stage Breast Cancer ◽  
Cardiac Events ◽  
Adjuvant Trastuzumab ◽  
Comorbidity Score ◽  
Days Of Therapy

Purpose Few data are available regarding adjuvant trastuzumab use in older women with early-stage breast cancer. We examined rates and predictors of adjuvant trastuzumab completion and cardiac events in this population. Patients and Methods We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data to identify patients age ≥ 66 years with stage I to III breast cancer diagnosed between 2005 and 2009 who received trastuzumab. Completion of trastuzumab was defined as receipt of more than 270 days of therapy. We used multivariable logistic regression to examine patient, clinical, and geographic characteristics associated with trastuzumab completion. We also examined rates of hospital admissions for cardiac events. Results Among 2,028 women, most (71.2%) were younger than age 76 years and had a comorbidity score of 0 (66.8%); 85.2% received trastuzumab with chemotherapy. Overall, 1,656 women (81.7%) completed trastuzumab. Older patients and those with more comorbidity had lower odds of treatment completion (odds ratio [OR], 0.40 [95% CI, 0.30 to 0.55] for age ≥ 80 years v age 66 to 70 years; OR, 0.65 [95% CI, 0.49 to 0.88] for comorbidity score of 2 v 0). During treatment, 73 patients (3.6%) were hospitalized for cardiac events (2.6% of those who completed trastuzumab v 8.1% of those who did not; P < .001). Conclusion Most older patients who initiated adjuvant trastuzumab completed therapy. Age and comorbidity were among factors that were associated with treatment completion, and rates of significant cardiac events were higher in those who did not complete therapy. Further exploration of toxicities and optimal treatments for older women with human epidermal growth factor receptor 2–positive breast cancer are warranted.

scholarly journals Feasibility and Cardiac Safety of Trastuzumab Emtansine After Anthracycline-Based Chemotherapy As (neo)Adjuvant Therapy for Human Epidermal Growth Factor Receptor 2–Positive Early-Stage Breast Cancer

2015 ◽  
Vol 33 (10) ◽  
pp. 1136-1142 ◽  
Author(s):  
Ian E. Krop ◽  
Thomas M. Suter ◽  
Chau T. Dang ◽  
Luc Dirix ◽  
Gilles Romieu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Trastuzumab Emtansine ◽  
Cardiac Safety ◽  
Cardiac Events ◽  
Her2 Positive ◽  
Epidermal Growth

Purpose Trastuzumab emtansine (T-DM1), an antibody–drug conjugate comprising the cytotoxic agent DM1, a stable linker, and trastuzumab, has demonstrated substantial activity in human epidermal growth factor receptor 2 (HER2) –positive metastatic breast cancer, raising interest in evaluating the feasibility and cardiac safety of T-DM1 in early-stage breast cancer (EBC). Patients and Methods Patients (N = 153) with HER2-positive EBC and prechemotherapy left ventricular ejection fraction (LVEF) ≥ 55% received (neo)adjuvant doxorubicin plus cyclophosphamide or fluorouracil plus epirubicin plus cyclophosphamide followed by T-DM1 for four cycles. Patients could then receive three to four cycles of optional docetaxel with or without trastuzumab. T-DM1 was then resumed with optional radiotherapy (sequential or concurrent) for 1 year (planned) of HER2-directed therapy. The coprimary end points were rate of prespecified cardiac events and safety. Results Median follow-up was 24.6 months. No prespecified cardiac events or symptomatic congestive heart failures were reported. Four patients (2.7%) had asymptomatic LVEF declines (≥ 10 percentage points from baseline to LVEF < 50%), leading to T-DM1 discontinuation in one patient. Of 148 patients who received ≥ one cycle of T-DM1, 82.4% completed the planned 1-year duration of HER2-directed therapy. During T-DM1 treatment, 38.5% and 2.7% of patients experienced grade 3 and 4 adverse events, respectively. Approximately 95% of patients receiving T-DM1 plus radiotherapy completed ≥ 95% of the planned radiation dose with delay ≤ 5 days. Conclusion Use of T-DM1 for approximately 1 year after anthracycline-based chemotherapy was feasible and generally well tolerated by patients with HER2-positive EBC, providing support for phase III trials of T-DM1 in this setting.

Short versus long duration of adjuvant trastuzumab (T) in HER2+ breast cancer: A systematic review and meta-analysis of randomized controlled trials (RCTs).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12057-e12057 ◽  
Author(s):  
Qurat Ul Ain Riaz Sipra ◽  
Irbaz Bin Riaz ◽  
Muhammad Husnain ◽  
Ammad Raina ◽  
Ahsan Khan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Early Stage ◽  
Meta Analysis ◽  
Unmet Need ◽  
Disease Free Survival ◽  
Significant Heterogeneity ◽  
Cardiac Events ◽  
Her2 Breast Cancer ◽  
Study Heterogeneity

e12057 Background: Several RCTs have evaluated a shorter duration of T ( < 12 months) with hopes of similar efficacy, reduced cardiotoxicity, cost and burden of treatment. Of the 5 major studies, PERSPHONE showed that 6 months was non-inferior compared to 12 months. However, four additional studies of shorter duration failed to demonstrate non-inferiority. Therefore, we performed an updated systematic review and a meta-analysis to assess the optimal duration of adjuvant T. Methods: MEDLINE, EMBASE, Cochrane, Scopus and conference proceedings were searched to identify RCTs comparing one year of adjuvant T with a shorter duration in early-stage HER2+ breast cancer. The DerSimonian-Laird random-effects Meta-Analysis was performed using CMAv3 software to derive pooled Hazard Ratio (HR) estimates for overall survival (OS, Disease-Free Survival (DFS) and Odds Ratio(OR) estimates of cardiac toxicity. Q-test was used to assess between-study heterogeneity; I2 statistic was computed to express the percentage of the total observed variability due to study heterogeneity. The risk for bias was assessed using the Cochrane Collaboration’s tool. Results: We screened 1772 citations and identified 5 studies(n = 11,377) for analysis. 5691 patients were randomized to 12 months of adjuvant T while 5686 were randomized to a shorter duration (3 studies evaluated 6 vs 12 months, 2 studies evaluated 9 weeks vs 12 months). OS (HR, 1.16, 95% CI 1.03-1.31, P= 0.015,I2 0.00, p= 0.837) and DFS (HR, 1.14, 95% CI 1.02-1.26 , P = 0.016,I2 14.90, p= 0.319) were significantly worse in patients receiving shorter duration T as compared to 12 months. Cardiotoxicity was significantly higher in the 12 month group vs shorter duration (OR, 2.10, 95% CI 1.58-2.80, p = 0.000 ,I2 51.182, p= 0.085). Grade 3/4 cardiac events and cardiac events leading to discontinuation of therapy were significantly higher in patients receiving 12 months (HR 2.06, 95% CI 1.60-2.63, P = 0.000, I2 3.967, p= 0.384). There was no significant heterogeneity among studies. Risk of bias was low. Conclusions: Twelve months of adjuvant T is associated with significantly better DFS and OS compared to a shorter duration. As such, 12 months should remain the standard of care for most patients. There is an unmet need to identify lower risk groups which might do well with from shorter duration of HER2-directed therapy.

Effect of IGF1R protein expression on benefit to adjuvant trastuzumab in early-stage HER2+ breast cancer in NCCTG N9831 trial.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 10503-10503 ◽  
Author(s):  
M. M. Reinholz ◽  
A. C. Dueck ◽  
B. Chen ◽  
X. Geiger ◽  
A. E. McCullough ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Early Stage ◽  
Adjuvant Trastuzumab ◽  
Her2 Breast Cancer
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