Anlotinib Combined With Chemotherapy and Neoadjuvant Therapy for Hormone Receptor-positive HER-2 Negative Breast Cancer (ACNTBC)

Anlotinib Plus Chemotherapy as Neoadjuvant Treatment of High-risk, Early-stage Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer: A Prospective, Single-arm, Single-center, Phase II Clinical Study

Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Combining anti-angiogenesis with chemotherapy yielded increased response rates in patients with early-stage human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This study aims to evaluate the efficacy and safety of adding anlotinib to standard neoadjuvant chemotherapy in primary (HER2)-negative breast cancer. Patients aged 18 years or older with previously untreated stage Ⅱ-III histologically documented (HER2)-negative breast cancer were assigned to receive chemotherapy plus oral Anlotinib. The primary endpoint was pathologic complete response (pCR) (no invasive carcinoma in breast or axilla). Secondary end points included safety and event-free survival (EFS).

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer Stage II
• Intervention / Treatment: Drug: Anlotinib

Detailed Description

Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Combining anti-angiogenesis with chemotherapy yielded increased response rates in patients with early-stage human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This phase II study aims to evaluate the efficacy and safety of adding anlotinib to standard neoadjuvant chemotherapy in primary (HER2)-negative breast cancer.

Patients aged 18 years or older with previously untreated stage Ⅱ-III histologically documented (HER2)-negative breast cancer were assigned to receive chemotherapy plus oral Anlotinib (12 mg qd, d1-14; 21 days per cycle; total 5 cycles). Chemotherapy comprised of pirarubicin at 50 mg/m2 and cyclophosphamide at 500 mg/m2 and albumin-bound paclitaxel at 200 mg/m2, (d1, 21 days per cycle; both total 6 cycles), which was then followed by surgery. The primary endpoint was pathologic complete response (pCR) (no invasive carcinoma in breast or axilla). Secondary end points included safety and event-free survival (EFS). Stratification was based on the clinical breast cancer stage .

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shannxi Province
    • Xi'an, Shannxi Province, China, 710032
      • Xijing Hospital Affiliated to Air Force Military Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All patients were HER2 negative, defi ned as immunohistochemistry of 0/1+, or if 2+, fluorescence in situ hybridisation showed no evidence of amplification of the HER2 gene.
• Patients were required to have a palpable primary tumor at least 2.0 cm in diameter in the breast, as assessed by physical examination, ultrasound, or magnetic resonance imaging. And to be classified as having tumor stage T1c to T4, nodal stage N0 to N3, (if patients having tumor stage of T1c, the nodal stage should be N1-3) and metastasis stage M0 (II-III stage).
• Other eligibility criteria adequate cardiac function (left ventricular ejection fraction within the normal institutional range, as assessed by multiple gated acquisition scan or echocardiogram), adequate bone marrow, hepatic, and renal function, and appropriate Eastern Cooperative Oncology Group (ECOG) performance status (0-1).
• All patients provided written informed consent.

Exclusion Criteria:

• Previously received anti-angiogenesis targeted drug therapy.
• patients have previous diagnosis of ischaemic heart disease, cerebrovascular disease, peripheral vascular disease, arterial or venous thromboembolic disease, cardiac failure, gastroduodenal ulcer, symptomatic diverticulitis, or inflammatory bowel disease.
• Previously received chemotherapy, radiotherapy, or endocrine therapy as treatment for breast cancer was allowed.
• No uncontrolled hypertension.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anlotinib; Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Anlotinib (12 mg qd, d1-14; 21 days per cycle; total 5 cycles) Combined TAC×6 cycles.	Drug: Anlotinib; Anlotinib (12 mg qd, d1-14; 21 days per cycle; total 5 cycles) Combined TAC×6 cycles: albumin-bound paclitaxel (200mg/m2, 1d Q3W) + pirarubicin （50mg/m2, 1d Q3W) + cyclophosphamide (500mg/m2, 1d Q3W); Other Names: TAC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response (pCR) Rate	Pathological complete response (pCR),which was also identified as total pCR (tpCR), was defined as the absence of invasive cancer in breast and no metastasis to regional lymph nodes (ypT0/is ypN0) in the surgical specimen after completion of neoadjuvant therapy, corresponding to Residual Cancer Burden (RCB) score of 0. Pathological response was evaluated by an independent pathologist blinded to treatment assignment on the resected breast specimen and axillary lymph nodes using H&E staining. The RCB grading system was used as the primary method to quantify residual disease. RCB I indicates minimal residual disease. RCB II indicates moderate residual disease. RCB III indicates extensive residual disease (worst outcome). Lower RCB scores represent better pathological response and are associated with improved long-term survival outcomes. tpCR was considered the most stringent and clinically meaningful endpoint for neoadjuvant studies, representing complete eradication of invasive tumor.	At definitive surgery, performed after completion of 6 cycles of neoadjuvant systemic therapy (approximately 18-24 weeks from treatment initiation).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RCB 0/I Rate	The outcome measure is defined as the proportion of participants who achieve a Residual Cancer Burden (RCB) class of 0 or I following neoadjuvant therapy and surgical resection. RCB score is calculated using the standardized RCB calculator. Pathological evaluation is performed on surgical specimens according to institutional or central laboratory guidelines. RCB 0: Pathologic complete response (pCR), defined as no residual invasive carcinoma in the breast primary tumor and ipsilateral axillary lymph nodes (in situ carcinoma allowed). RCB I: Minimal residual tumor burden, indicating extensive tumor regression with only minor residual disease.	At definitive surgery, performed after completion of 6 cycles of neoadjuvant systemic therapy (approximately 18-24 weeks from treatment initiation).
Number of Participants With Treatment-Related Adverse Events (TRAEs)	For safety evaluation, the severity grade (according to National Cancer Institute Common Terminology Criteria for Adverse Events, v 5.0) and the relationship to study treatment of AEs were assessed by physical examination and laboratory tests before and after every cycle, during follow-up visits, and upon indication by symptoms.	From first dose of study treatment through completion of neoadjuvant therapy and postoperative assessment, up to approximately 24-30 weeks per participant
EFS	EFS(Event-free survival)	Long-term follow-up schedule for disease status and survival entailed evaluations every 3 months in the first 2 years after surgery, every 6 months for the subsequent three years, and then annually thereafter until the 10th year.
bpCR Rate	The outcome measure is defined as the proportion of participants who achieve breast pathologic complete response (bpCR) following neoadjuvant therapy and surgical resection. bpCR is defined as no residual invasive carcinoma in the breast primary tumor (residual ductal carcinoma in situ [DCIS] is allowed), regardless of axillary lymph node status.	At definitive surgery, performed after completion of 6 cycles of neoadjuvant systemic therapy (approximately 18-24 weeks from treatment initiation).
apCR Rate	The outcome measure is defined as the proportion of participants who achieve axillary pathologic complete response (apCR) following neoadjuvant therapy and surgical resection. apCR is defined as no residual invasive carcinoma in the ipsilateral axillary lymph nodes, regardless of breast primary tumor status.	At definitive surgery, performed after completion of 6 cycles of neoadjuvant systemic therapy (approximately 18-24 weeks from treatment initiation).

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Investigators: Principal Investigator: Ting Wang, PhD, Xijing Hospital Affiliated to Air Force Military Medical University

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2022
• Primary Completion (Actual): August 15, 2024
• Study Completion (Estimated): July 30, 2028

Study Registration Dates

• First Submitted: July 19, 2022
• First Submitted That Met QC Criteria: September 25, 2022
• First Posted (Actual): September 28, 2022

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Breast cancer Antivascular drugs Neoadjuvant therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; anlotinib
• Other Study ID Numbers: KY20202075-F-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No