Breast Cancer Stage II
Conditions
Keywords
Breast cancer Antivascular drugs Neoadjuvant therapy
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).
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 .
Interventions
DRUGAnlotinib
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);
Sponsors
Xijing Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Check all roles that are masked or check None.
Intervention model description
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.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR) Rate | At definitive surgery, performed after completion of 6 cycles of neoadjuvant systemic therapy (approximately 18-24 weeks from treatment initiation). | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| RCB 0/I Rate | At definitive surgery, performed after completion of 6 cycles of neoadjuvant systemic therapy (approximately 18-24 weeks from treatment initiation). | 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. |
| 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 | 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. |
| 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. | EFS(Event-free survival) |
| bpCR Rate | At definitive surgery, performed after completion of 6 cycles of neoadjuvant systemic therapy (approximately 18-24 weeks from treatment initiation). | 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. |
| apCR Rate | At definitive surgery, performed after completion of 6 cycles of neoadjuvant systemic therapy (approximately 18-24 weeks from treatment initiation). | 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. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORTing Wang, PhD
Xijing Hospital Affiliated to Air Force Military Medical University
Participant flow
Pre-assignment details
After providing informed consent, patients underwent baseline assessments including physical examination, breast MRI, core needle biopsy for histological confirmation, and immunohistochemistry staining for ER, PR, HER2, and Ki-67. Eligibility was confirmed based on theinclusion and exclusion criteria. Patients who met all inclusion criteria and none of the exclusion criteria were enrolled and assigned to receive study treatment.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 46 years |
| Lymph Node Status (N stage) N0 | 5 Participants |
| Lymph Node Status (N stage) N1 | 11 Participants |
| Lymph Node Status (N stage) N2 | 6 Participants |
| Lymph Node Status (N stage) N3 | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 31 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment China | 31 participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 0 Participants |
| Tumor size (T stage) T1 | 1 Participants |
| Tumor size (T stage) T2 | 19 Participants |
| Tumor size (T stage) T3 | 8 Participants |
| Tumor size (T stage) T4 | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 31 |
| other Total, other adverse events | 31 / 31 |
| serious Total, serious adverse events | 0 / 31 |
Outcome results
None listed