• Adjuvant/Neoadjuvant Therapy
• Oncology Clinical Trials
• Breast Cancer

• Oncology
• Adjuvant/Neoadjuvant Therapy
• Oncology Clinical Trials
• Breast Cancer

Günther Steger, MD, Medical University of Vienna, Vienna, Austria, presented data from a study demonstrating that neoadjuvant docetaxel (D) plus trastuzumab (H), DH plus bevacizumab (B; DHB), DH plus nonpegylated liposomal doxorubicin (N; DHN), and DHNB treatment regimens are feasible and can be safely administered to patients with early HER2-positive breast cancer.

According to Prof Steger, neoadjuvant treatment regimens resulting in high pathologic complete response (pCR) rates are needed for patients with HER2-positive breast cancer because they are correlated with favorable prognoses. Although N in combination with H is highly effective in HER2-positive breast cancer, this regimen is unsuitable because of high cardiotoxicity. HER2-positive breast cancer cells have, however, been shown to produce high levels of vascular endothelial growth factor, he added.

Consequently, the Phase 2 Study of Neoadjuvant Trastuzumab + Docetaxel + Non-pegylated Liposome-Encapsulated Doxorubicin (NPLD) ± Bevacizumab in HER2-Positive Early Breast Cancer [ABCSG-32; NCT01367028] was conducted to evaluate the cardiotoxicity and efficacy of N and B in combination with DH in the neoadjuvant treatment of early HER2-positive breast cancer.

Inclusion criteria included patients ≥ 18 years with (1) pathologically confirmed invasive primary breast adenocarcinoma, with or without palpable lymph nodes, who were scheduled for taxane-containing neoadjuvant systemic therapy and (2) HER2 protein overexpression as determined by immunohistochemistry 3 + or by HER2 (c-erbB2) gene amplification according to fluorescent in situ hybridization or chromogenic in situ hybridization of the primary tumor. Exclusion criteria included patients with metastatic disease, HER2-negative disease, or a history of prior local or systemic antitumor therapy.

This open-label phase 2 trial enrolled 100 patients with biopsy-proven, invasive, early HER2-positive breast cancer who were randomized to 6 cycles (every 21 days) of the following:

• DH: D (100 mg/m²) + H (8/6 mg/kg; n = 25)

• DHB: DH + B (15 mg/kg; n = 25)

• DHN: D (75 mg/m²) + H + N (50 mg/m²; n = 26)

• DHNB: D (75 mg/m²) + H + N + B (15 mg/m²; n = 24)

All patients received pegfilgrastim (6 mg, subcutaneously) on day 2.

Cardiotoxicity was low in all 4 regimens, with only 3 cardiac toxicity events documented (DH, n = 0; DHB, DHN, and DHNB, all n = 1). A cardiac toxicity event was defined as the occurrence of symptomatic left ventricular dysfunction, NYHA class 2 to 4; an asymptomatic drop of ejection fraction > 15% from baseline or < 50%; or the appearance of significant arrhythmias requiring treatment.

Although noncardiac toxicity was also acceptable, it was more pronounced in patients receiving the 3- and 4-drug combinations (Table 1).

All 4 regimens were highly effective. The overall pCR rate was 52%, with 63% and 62% of patients experiencing pCR in the DHN and DHNB regimens, respectively. The total pCR rate was also highest after DHN (58%) and DHNB (57%).

Prof Steger concluded that neoadjuvant DH, DHB, DHN, and DHNB can be safely administered to patients with HER2-positive early breast cancer. He emphasized, however, that although noncardiac toxicity is acceptable, its increase with the 3- and 4-drug combinations may lead to early treatment termination in some patients.

• © 2014 MD Conference Express®