Cardiac safety of docetaxel/cyclophosphamide/trastuzumab (DCH) as adjuvant therapy for HER-2 (+) early stage breast cancer

Abstract

e11577 Background: The addition of trastuzumab to adjuvant chemotherapy is standard for Her2(+) breast cancer. In our practice, adjuvant docetaxel/cyclophosphamide (DC) + 1 yr of trastuzumab is offered to pts with low-risk Her2(+) disease. Although the HERA trial allowed the use of a variety of chemotherapy regimens to combine with trastuzumab, it predates the acceptance of DC as an adjuvant care-standard and therefore the safety profile of DCH has not been reported. Methods: We conducted a two-center, retrospective cohort study including all pts treated with adjuvant DCH between 12/06 and 3/08 to assess its safety profile. Using the CTCAE criteria, records were screened for toxicity from DCH initiation to the present. The primary outcome was cardiac toxicity defined as clinical CHF or a confirmed significant LVEF decline (≥ 16% decrease in EF from baseline or EF < 50% + ≥ 10% decrease from baseline). Results: 27 pts, mean age 54, were identified with a median follow-up of 23.4 months (range 12.2- 42.0 months). The mean tumor size was 1.4 cm (0.5–4.3 cm) with 84% hormone receptor(+), 96% node(-) and 100% Her2(+) by FISH or IHC. 52% of pts received DCH concurrently and 48% received trastuzumab following DC. Baseline mean EF was 65% (53–86%). EF assessments were performed every 3 months/pt. 7.4% and 11.1% of pts had a prior history of anthracycline exposure or cardiac disease respectively. 11.1% of pts experienced a significant LVEF decline occurring on ≥ 2 sequential EF measurements. The trastuzumab discontinuation rate was 3.7% (1 pt). No pt developed clinical CHF. 88% of pts have now completed trastuzumab therapy. 33% of pts received pegfilgrastim with chemotherapy. 25% of pts experienced grade III-IV neutropenia. Grade III-IV anemia and thrombocytopenia were not observed. Trastuzumab-related infusion reactions were observed in 1 pt and did not warrant drug discontinuation. At this time all pts are alive and no patient has experienced disease recurrence. Conclusions: The DCH regimen, given in sequence or concomitantly, appears to be a safe and effective adjuvant treatment for women with Her2(+) disease. Along with docetaxel/carboplatin/trastuzumab, DCH represents another acceptable non-anthracycline containing regimen for low-risk, Her2(+) pts. No significant financial relationships to disclose.