Low Cardiac Toxicity With Adjuvant Non-Anthracycline Plus Trastuzumab In Breast Cancer

Researchers suggest that serial cardiac monitoring during treatment with adjuvant paclitaxel plus trastuzumab could be restricted to breast cancer patients at high risk of cardiac toxicity

medwireNews: The incidence of severe left ventricular systolic dysfunction (LVSD) and asymptomatic reduction in left ventricular ejection fraction (LVEF) is low in early-stage breast cancer patients treated with adjuvant paclitaxel and trastuzumab , research suggests.

“The favourable cardiovascular safety profile of trastuzumab in this non-anthracycline setting suggests that baseline LVEF assessment may be sufficient for the majority of patients, with serial LVEF assessments reserved for patients considered at a higher risk for cardiac toxic effects”, say Chau Dang, from Memorial Sloan Kettering Cancer Center in New York, USA, and co-workers.

They conducted a secondary analysis of data from a trial in which 406 patients were given concurrent weekly paclitaxel plus trastuzumab for 12 weeks, followed by trastuzumab alone for 39 weeks, delivered at a dose of either 2 mg/kg weekly or 6 mg/kg every 3 weeks. The study participants had stage I or II breast cancer that was positive for human epidermal growth factor receptor 2. They were either node negative or had micrometastasis in a lymph node and had tumours no larger than 3 cm.

Grade 3 LVSD occurred in two (0.5%) patients, who developed symptomatic congestive heart failure resulting in trastuzumab discontinuation at 6 months and 11 months after starting study treatment. The researchers note that the cardiac symptoms resolved in both cases with appropriate treatment.

Moreover, 13 (3.2%) participants developed significant asymptomatic LVEF decline that led to interruption of trastuzumab therapy. In three patients, the LVEF decline was persistent and two stopped trastuzumab therapy, while one remained on treatment, which the study authors say was a protocol violation.

LVEF, as assessed by transthoracic echocardiogram or radionuclide multigated acquisition scan, remained consistent through the course of the study in the overall study population, at a median of 65% at baseline and 64% at 12 weeks and 6 and 12 months.

In light of the low incidence of cardiac dysfunction, Chau Dang et al conclude in JAMA Oncology that “our findings suggest that LVEF monitoring during trastuzumab therapy without anthracyclines could be simplified for many individuals.”

In a related editorial, Gérard Milano, from Centre Antoine-Lacassagne in Nice, France, and co-authors underscore the relevance of studying the cardiac toxic effects of this regimen, as “it could well become the standard of care for low-risk patients with breast cancer” given the primary findings, of a 3-year disease-free survival rate of 98.7%, previously reported on oncologyPro .

However, they also highlight some limitations, including the lack of standardisation of LVEF quantification, inconsistency in collecting data on cardiovascular risk factors and lack of data on body mass index, nicotine intoxication and menopausal status.

Gérard Milano et al conclude: “A prospective, properly designed, confirmatory study focused on the cardiac impact of this treatment remains necessary to obtain more precise information on these adverse effects.”

References

Dang C, 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 2015; Advance online publication 05 November. doi:10.1001/jamaoncol.2015.3709

Milano G, Chamorey E, Ferrero J-M. Trastuzumab and Cardiac Outcomes in Breast Cancer. A Story We Know by Heart? JAMA Oncol 2015; Advance online publication 05 November. doi:10.1001/jamaoncol.2015.3866

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