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. 2024 Feb 29;36(1):55-65.
doi: 10.21147/j.issn.1000-9604.2024.01.06.

Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase II single-arm study

Yaping Yang  1 , Liang Jin  1 , Yudong Li  1 , Nanyan Rao  1 , Chang Gong  1 , Shunrong Li  1 , Jiannan Wu  1 , Jinghua Zhao  1 , Linxiaoxiao Ding  1 , Fengxia Gan  1 , Jun Zhang  2 , Ruifa Feng  3 , Zhenzhen Liu  4 , Qiang Liu  1
Affiliations

Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase II single-arm study

Yaping Yang et al. Chin J Cancer Res. .

Abstract

Objective: Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin (PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2 (HER2)-positive early breast cancer (BC).

Methods: In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD (30-35 mg/m2) and cyclophosphamide (600 mg/m2), followed by four cycles of taxanes (docetaxel, 90-100 mg/m2 or nab-paclitaxel, 260 mg/m2), concomitant with eight cycles of trastuzumab (8 mg/kg loading dose, then 6 mg/kg) and pertuzumab (840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0). Secondary endpoints included breast pCR (bpCR), objective response rate (ORR), disease control rate, rate of breast-conserving surgery (BCS), and safety (with a focus on cardiotoxicity).

Results: Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42 (53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval (95% CI), 48.5%-71.2%] patients achieved tpCR, and 49 (62.8%) achieved bpCR. ORRs were 76.9% (95% CI, 66.0%-85.7%) and 93.6% (95% CI, 85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine (11.5%) patients experienced asymptomatic left ventricular ejection fraction (LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP (NT-proBNP), troponin I, or high-sensitivity troponin.

Conclusions: This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile, especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.

Keywords: Breast cancer; HER2-positive breast cancer; dual HER2 blockade; neoadjuvant therapy; sequential therapy.

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Figures

Figure 1
Figure 1
Treatment schedule. PLD, pegylated liposomal doxorubicin; pCR, pathological complete response.
Figure 2
Figure 2
Study profile. PLD, pegylated liposomal doxorubicin; C, cyclophosphamide; T, taxanes; H, trastuzumab; P, pertuzumab.
Figure 3
Figure 3
Tumor response in evaluable patients. (A) Waterfall plot of maximum percent change in target lesion size from baseline in evaluable patients per RECIST 1.1; (B) Response time and treatment duration. Each bar represents a patient.
Figure S1
Figure S1
LVEF changes during neoadjuvant treatment. LVEF, left ventricular ejection fraction.
See this image and copyright information in PMC

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