Abstract P5-20-17: Safety of continuing chemotherapy in overt left ventricular dysfunction using antibodies to human epidermal growth factor receptor-2: A retrospective study
Authors: Bharaj UK , Leong D , Dhesy-Thind S , Ellis P , Mukherjee S , Bordeleau L , Phillips C , Brown M , Kumar Tyagi N 
Published: February 2018

Introduction: Trastuzumab is a monoclonal antibody that targets the human epidermal growth factor receptor (HER)-2 and significantly improves survival in HER-2 positive early stage breast cancer. However, trastuzumab is also known to cause cardiotoxicity. Guidelines recommend withholding or discontinuing trastuzumab if left ventricular ejection fraction (LVEF) falls ≥15% from baseline, or to &lt;50%, but there is little evidence to support this strategy. Additionally, premature discontinuation of trastuzumab may lead to poorer cancer outcomes. Trastuzumab cardiotoxicity is frequently reversible, and the use of angiotensin converting enzyme-inhibitors (ACE-I) and beta blockers is highly effective at treating impaired LVEF in other patient populations. We therefore hypothesize that it is safe to continue trastuzumab in patients with asymptomatic or mildly symptomatic fall in LVEF, when concomitantly treated with ACE-I and beta blockers.

Methods: In this retrospective chart review, we identified 18 consecutive patients with stage 1-3 HER-2 positive breast cancer patients who had a decline in LVEF meeting the criteria above to withhold trastuzumab, and who were referred to our cardio-oncology service from the beginning of 2015 to March 2017. These patients were offered and consented to receive ongoing trastuzumab accompanied by ACE-I and/or beta blocker. Data on patient demographics, cancer therapies, clinical features, LVEF, and cardiac medications were extracted from medical charts.

Results: Among the 18 patients identified, all were women, 12 (67%) were estrogen receptor positive, and 7 progesterone receptor positive (39%). 11 (61%) of patients had a left-sided breast cancer, 6 (33%) had right-sided breast cancer, and 1 (5%) had an unspecified side breast cancer. 17 (94%) of patients had previously undergone radiation therapy, and 4 (22%) had experienced a recurrence. 16 patients had received a prior anthracycline regimen (10 sequentially, 6 concurrently). The patients were treated with one or a combination of the following medications: carvedilol (n=13), ramipril (n=12), bisoprolol (n=1), candesartan (n=2), rosuvastatin (n=2), atorvastatin (n=2). The patients were followed up for an average of 7 months after starting cardiac therapy. Table 1 summarizes the mean±SD LVEF values over the follow up time period. All patient except one (94%) completed trastuzumab treatment successfully. This patient with concomitant moderate-severe mitral regurgitation was hospitalized for pulmonary edema. Trastuzumab was discontinued and LVEF has subsequently returned to normal values.

Table 1: LVEF progression from baseline to end of follow-upMean±SD LVEF at baseline57.59±5.49%Mean±SD LVEF on referral to cardio-oncology clinic50.75±4.76%Mean±SD LVEF at end of follow-up56.35±3.50%

Conclusion: Treating cardiac dysfunction related to trastuzumab in a cardio-oncology clinic, using beta blockers and ACE-I may enable completion of trastuzumab therapy. Randomized trials are necessary before it can be widely recommended, however findings from our experience suggest this may be a promising new treatment strategy.

Citation Format: Bharaj UK, Leong D, Dhesy-Thind S, Ellis P, Mukherjee S, Bordeleau L, Phillips C, Brown M, Kumar Tyagi N. Safety of continuing chemotherapy in overt left ventricular dysfunction using antibodies to human epidermal growth factor receptor-2: A retrospective study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-20-17.