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Clinical Trial
. 2024 Jan 5;29(1):e15-e24.
doi: 10.1093/oncolo/oyad160.

A Phase II Study of Neoadjuvant PLD/Cyclophosphamide and Sequential nab-Paclitaxel Plus Dual HER2 Blockade in HER2-Positive Breast Cancer

Ji-Xin Yang  1 , Yu-Qing Yang  1 , Wen-Yu Hu  1 , Lu Yang  1 , Jiang Wu  1 , Xin-Xin Wen  1 , Jing Yu  1 , Mei-Ling Huang  1 , Dong-Dong Xu  1 , Dan-Chen Tie  1 , Lei Wang  1 , Fan-Fan Li  2 , Nan-Lin Li  1
Affiliations
Clinical Trial

A Phase II Study of Neoadjuvant PLD/Cyclophosphamide and Sequential nab-Paclitaxel Plus Dual HER2 Blockade in HER2-Positive Breast Cancer

Ji-Xin Yang et al. Oncologist. .

Abstract

Background: Neoadjuvant trastuzumab/pertuzumab (HP) plus chemotherapy for HER2-positive breast cancer (BC) achieved promising efficacy. The additional cardiotoxicity still existed. Brecan study evaluated the efficacy and safety of neoadjuvant pegylated liposomal doxorubicin (PLD)/cyclophosphamide and sequential nab-paclitaxel based on HP (PLD/C/HP-nabP/HP).

Patients and methods: Brecan was a single-arm phase II study. Eligible patients with stages IIA-IIIC HER2-positive BC received 4 cycles of PLD, cyclophosphamide, and HP, followed by 4 cycles of nab-paclitaxel and HP. Definitive surgery was scheduled after 21 days for patients completing treatment or experiencing intolerable toxicity. The primary endpoint was the pathological complete response (pCR).

Results: Between January 2020 and December 2021, 96 patients were enrolled. Ninety-five (99.0%) patients received 8 cycles of neoadjuvant therapy and all underwent surgery with 45 (46.9%) breast-conserving surgery and 51 (53.1%) mastectomy. The pCR was 80.2% (95%CI, 71.2%-87.0%). Four (4.2%) experienced left ventricular insufficiency with an absolute decline in LVEF (43%-49%). No congestive heart failure and ≥grade 3 cardiac toxicity occurred. The objective response rate was 85.4% (95%CI, 77.0%-91.1%), including 57 (59.4%) complete responses and 25 (26.0%) partial responses. The disease control rate was 99.0% (95%CI, 94.3%-99.8%). For overall safety, ≥grade 3 AEs occurred in 30 (31.3%) and mainly included neutropenia (30.2%) and asthenia (8.3%). No treatment-related deaths occurred. Notably, age of >30 (P = .01; OR = 5.086; 95%CI, 1.44-17.965) and HER2 IHC 3+ (P = .02; OR = 4.398; 95%CI, 1.286-15.002) were independent predictors for superior pCR (ClinicalTrials.gov Identifier NCT05346107).

Conclusion: Brecan study demonstrated the encouraging safety and efficacy of neoadjuvant PLD/C/HP-nabP/HP, suggesting a potential therapeutic option in HER2-positive BC.

Keywords: HER2 positive; breast cancer; dual HER2 blockade; neoadjuvant therapy; pegylated liposomal doxorubicin (PLD).

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Conflict of interest statement

The authors indicated no financial relationships.

Figures

Figure 1.
Figure 1.
Treatment schedule. The treatment procedures for patients with HER2-positive breast cancer. PLD = pegylated liposomal doxorubicin, HER2 = human epidermal growth factor receptor 2, pCR = pathological complete response.
Figure 2.
Figure 2.
Trial profile. ITT = intention-to-treat, SAS = safety analysis set.
Figure 3.
Figure 3.
Tumor response. Waterfall plot of tumor size change from baseline to maximum percentage in each patient as per RECIST version 1.1. CR, complete response; PR, partial response; PD, progressive disease; SD, stable disease.
Figure 4.
Figure 4.
Left ventricular ejection fraction (LVEF) changes during neoadjuvant treatment in the intent-to-treat population.
See this image and copyright information in PMC

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