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. 2023 Mar 31;11(6):243.
doi: 10.21037/atm-22-4093. Epub 2023 Feb 13.

Neoadjuvant Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) and chemotherapy versus placebo plus chemotherapy in patients with HER2-negative breast cancer: a randomized, controlled, double-blind trial

Yue Gong #  1   2   3 , Hua Zuo #  1   2   3   4 , Ying Zhou  1   2   3 , Ke-Da Yu  1   2   3 , Guang-Yu Liu  1   2   3 , Gen-Hong Di  1   2   3 , Jiong Wu  1   2   3 , Zhe-Bin Liu  1   2   3 , Zhi-Ming Shao  1   2   3
Affiliations

Neoadjuvant Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) and chemotherapy versus placebo plus chemotherapy in patients with HER2-negative breast cancer: a randomized, controlled, double-blind trial

Yue Gong et al. Ann Transl Med. .

Abstract

Background: According to preclinical experiments, Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) exerts antiproliferative effects against breast cancer cells. It has been approved by the State Food and Drug Administration in China for complementary cancer treatment, and its safety has been confirmed in previous clinical trials. The present randomized, controlled, double-blind clinical trial was conducted to investigate the efficacy and safety of neoadjuvant PA-MSHA and placebo with chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

Methods: Eligible patients aged 18 years or older with previously untreated HER2-negative stage II-III breast cancer were enrolled and randomly assigned at a 1:1 ratio to receive neoadjuvant chemotherapy with PA-MSHA or a placebo. The Response Evaluation Criteria in Solid Tumors (RECIST) was used to assess clinical response every 2 cycles. The primary endpoint was the objective response rate (ORR) based on the clinical response following neoadjuvant chemotherapy.

Results: A total of 75 patients were randomly assigned to either the PA-MSHA group (37 patients) or the control group (38 patients). The ORR was found to be significantly higher in the PA-MSHA group compared with the control group [86.5% versus 60.5%; rate difference 26.0; 95% confidence interval (CI): 5.9-43.5%; P=0.011]. The pathological complete response (pCR) and survival outcomes did not differ significantly between the 2 groups. Patients with immune-related adverse events (irAEs) appeared to benefit from the PA-MSHA treatment, with greater disease-free, relapse-free, and overall survival. The application of PA-MSHA to neoadjuvant chemotherapy did not increase the incidence of severe adverse events. Moreover, the addition of PA-MSHA increased serum interferon-γ levels and the percentage of peripheral blood T cells, CD8+/CD4+ T cells, CD8+CD28+ T cells, and natural killer (NK) cells, and decreased serum interleukin 4 levels.

Conclusions: The addition of PA-MSHA to neoadjuvant chemotherapy is an effective alternative regimen for HER2-negative breast cancer. Patients with irAEs caused by PA-MSHA may obtain more benefits from this treatment.

Trial registration: Chinese Clinical Trial Registry ChiCTR-TRC-10000794.

Keywords: HER2-negative breast cancer; Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA); clinical trial; efficacy; neoadjuvant chemotherapy.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4093/coif). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
CONSORT diagram of the trial. ITT, intention to treat; PA-MSHA, Pseudomonas aeruginosa mannose-sensitive hemagglutinin; PCb, paclitaxel and carboplatin.
Figure 2
Figure 2
Kaplan-Meier plots of disease-free survival (A), relapse-free survival (B), overall survival (C), and distant disease-free survival (D) between the 2 treatment groups. HR, hazard ratio; CI, confidence interval; PA-MSHA, Pseudomonas aeruginosa mannose-sensitive hemagglutinin; PCb, paclitaxel and carboplatin.
Figure 3
Figure 3
Kaplan-Meier plots of disease-free survival (A), relapse-free survival (B), overall survival (C), and distant disease-free survival (D) according to irAEs. irAEs, immune-related adverse events; PA-MSHA, Pseudomonas aeruginosa-mannose-sensitive hemagglutinin.
Figure 4
Figure 4
Comparison of the percentage of peripheral blood T cells (A), ratio of CD4+/CD8+ T cells (B), CD8+CD28+ T cells (C), and NK cells (D) at baseline and posttreatment, as well as the absolute change during the neoadjuvant treatment between the 2 treatment groups. *, P<0.05; **, P<0.01. NS, not significant; PCb, paclitaxel and carboplatin; PA-MSHA, Pseudomonas aeruginosa mannose-sensitive hemagglutinin; NK, natural killer.
Figure 5
Figure 5
Comparison of serum levels of IFN-γ (A), IL-4 (B) and the ratio of IFN-γ/IL-4 (C) at baseline and posttreatment, as well as the absolute change during the neoadjuvant treatment between the 2 treatment groups. *, P<0.05; ***, P<0.001. IFN, interferon; NS, not significant; IL, interleukin; NS, not significant; PA-MSHA, Pseudomonas aeruginosa mannose-sensitive hemagglutinin; PCb, paclitaxel and carboplatin.
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