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

NCT05558722 | Active Not Recruiting Phase 2 Results DMC

• 1 other identifier: KY20202075-F-2
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Breast Cancer Stage II

Keywords

Breast cancer Antivascular drugs Neoadjuvant therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• RCB 0/I Rate

  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)

  From first dose of study treatment through completion of neoadjuvant therapy and postoperative assessment, up to approximately 24-30 weeks per participant

• EFS

  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

  At definitive surgery, performed after completion of 6 cycles of neoadjuvant systemic therapy (approximately 18-24 weeks from treatment initiation).

• apCR Rate

  At definitive surgery, performed after completion of 6 cycles of neoadjuvant systemic therapy (approximately 18-24 weeks from treatment initiation).

Study Arms (1)

Anlotinib

EXPERIMENTAL

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

Interventions

Anlotinib DRUG

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);

Also known as: TAC

Anlotinib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Xijing Hospital: lead

Study Sites (1)

Xijing Hospital Affiliated to Air Force Military Medical University

Xi'an, Shannxi Province, 710032, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

anlotinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Limitations and Caveats

The inherent single-arm, non-randomized design and the limited sample size affect the reliability of efficacy

Results Point of Contact

• Title: Ting Wang
• Organization: Department of Thyroid, Breast, and Vascular Surgery, Xijing Hospital, the Fourth Military Medical University

ting_w100@126.com

+86 029 84775271

Study Officials

• Ting Wang, PhD

  Xijing Hospital Affiliated to Air Force Military Medical University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Check all roles that are masked or check None.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 19, 2022
• First Posted: September 28, 2022
• Study Start: December 5, 2022
• Primary Completion: August 15, 2024
• Study Completion (Estimated): July 30, 2028
• Last Updated: June 10, 2026
• Results First Posted: June 10, 2026

Record last verified: 2026-04

Locations

CN (1)