The goal of this clinical trial is to evaluate the efficacy and safety of neoadjuvant stereotactic body radiotherapy (SBRT) followed by nab-paclitaxel combined with toripalimab in patients with previously untreated HR+/HER2-negative breast cancer. Eligible patients include those with stage IIB-IIIC disease (cT3N0, cT2-4N1-3 or cT1N2-3) or stage IIA disease (cT2N0 or cT1N1) with at least two of the following high-risk factors: histologic grade 3, Ki-67 ≥50% or premenopausal with age \<50 years. A total of 27 enrolled patients will be assigned to receive the combination therapy. The primary question it aims to answer is whether this combination of radiotherapy, de-escalated chemotherapy, and immunotherapy can improve the total pathologic complete response (tpCR) rate (defined as ypT0/Tis ypN0).
HR-positive and HER2-negative (HR+/HER2-) breast cancer is the most common subtype of breast cancer. Although this subtype is generally associated with favorable overall survival, patients with high-risk features remain at substantial risk for late recurrence and distant metastasis. In particular, those presenting with large primary tumors (cT3 or higher) or axillary lymph node involvement face a significantly elevated risk of locoregional recurrence and distant metastasis relative to patients with earlier-stage, lower-risk disease. In recent years, the role of neoadjuvant therapy in the comprehensive treatment of breast cancer has gained increasing attention. The pathological complete response (pCR) rate following neoadjuvant therapy is closely associated with long-term survival. However, compared to HER2+ or triple-negative breast cancer, HR+/HER2- breast cancer patients exhibit a significantly lower pCR rate with neoadjuvant chemotherapy alone. Neoadjuvant chemotherapy combined with immunotherapy has become a key treatment strategy for TNBC, this combination also improves pCR rates in HR+/HER2- breast cancer, though the benefit is less pronounced than in TNBC. Radiotherapy not only releases a large number of tumor antigens and inflammatory signals to enhance systemic anti-tumor immune responses, but also promotes the exposure of tumor cell surface antigens, thereby increasing the immunogenicity of the tumor microenvironment. The synergistic effect of radiotherapy and immunotherapy, when combined with chemotherapy, may further improve treatment efficacy. Based on these, we designed this clinical trial evaluating the effect of neoadjuvant radiotherapy combined with de-escalated chemotherapy and immunotherapy, aiming to explore its potential to improve pCR rates and long-term outcomes in HR+/HER2- breast cancer patients. Enrolled patients will receive four cycles of single-agent Nab-Paclitaxel plus Toripalimab within one week after stereotactic radiotherapy, followed by surgery and subsequent adjuvant therapy. Postoperative pCR rate and prognosis of participants will be analyzed in our clinical study.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
27
The prescribed dose of radiation is 24 Gy delivered in 3 fractions (8 Gy/fraction) using SBRT technique. Subjects received SBRT for the primary breast cancer lesion at 8Gy/Fraction each time for 3 consecutive days, 1 week before the start of systemic therapy. The first day of radiation is C1D1.
Toripalimab will be administered at a fixed dose of 240 mg via intravenous infusion every 3 weeks (q3w). The first dose is given on Cycle 2 Day 1 (C2D1), followed by dosing on the first day of each subsequent cycle for a total of 4 cycles. (Toripalimab×4 240mg D1 q3w)
Combined with Toripalimab, Nab-paclitaxel will be dosed at 125 mg/m² based on body surface area, administered by intravenous infusion weekly (Days 1, 8, 15 of each 21-day cycle) for 4 cycles.(T×4, Nab-Paclitaxel 125mg/m2,D1、D8、D15 q3w).
Surgery will be performed 2-6 weeks after completion of neoadjuvant therapy. The surgical approach will be determined by the investigator based on disease status and patient preference.
The anthracycline may be either Epirubicin (body surface area-adjusted 50 mg/m²) or Liposomal Doxorubicin (body surface area-adjusted 30 mg/m²) combined with Cyclophosphamide (body surface area-adjusted 600 mg/m²). Both drugs were administered intravenously every 3 weeks, and then the first day of each course was administered for 4 cycles. (EC×4, Epirubicin 50 mg/m² or Liposomal Doxorubicin 30 mg/m², comined with Cyclophosphamide 600 mg/m², D1, q3w)
Conventional radiotherapy will be delivered to the breast/chest wall and regional lymph nodes (investigator-selected technique), with explicit prohibition of tumor bed boost irradiation.
Investigator-selected adjuvant endocrine therapy will be deterimend according to applicable guidelines, considering menopausal status, recurrence risk, treatment history, comorbidities as well as patient preference.
Xijing Hospital Affiliated to Air Force Military Medical University
Xi'an, Shannxi Province, China
RECRUITINGXijing Hospital Affiliated to Air Force Military Medical University
Xi'an, Shannxi, China
RECRUITINGTotal pathologic complete response (tpCR) rate according to RCB system
tpCR is defined as the absence of invasive carcinoma in the breast primary lesion and negative regional lymph nodes (ypT0/Tis ypN0) by hematoxylin-eosin staining after completion of the neoadjuvant treatment. RCB system will be used for the pathological evaluation after neoadjuvant therapy
Time frame: At definitive surgery, following completion of neoadjuvant SBRT and 4 cycles of nab-paclitaxel plus toripalimab (each cycle is 21 days), approximately 4 months from start of neoadjuvant therapy.
RCB 0/I rate
The RCB 0/I rate is defined as the percentage of patients achieving either pathological complete response (RCB-0) or minimal residual disease (RCB-I), corresponding to near-pCR status
Time frame: At definitive surgery, following completion of neoadjuvant SBRT and 4 cycles of nab-paclitaxel plus toripalimab (each cycle is 21 days), approximately 4 months from start of neoadjuvant therapy.
Breast pathologic complete response (bpCR) rate
bpCR is defined as the absence of residual invasive carcinoma in the breast primary lesion (ypT0/Tis; ductal carcinoma in situ may be present), regardless of regional lymph node status, assessed by hematoxylin and eosin (H\&E) staining after neoadjuvant therapy.
Time frame: At definitive surgery, following completion of neoadjuvant SBRT and 4 cycles of nab-paclitaxel plus toripalimab (each cycle is 21 days), approximately 4 months from start of neoadjuvant therapy.
Axillary pathologic complete response (apCR) rate
apCR is defined as negative pathologic status of axillary lymph nodes (ypN0) after neoadjuvant therapy, assessed by H\&E staining.
Time frame: At definitive surgery, following completion of neoadjuvant SBRT and 4 cycles of nab-paclitaxel plus toripalimab (each cycle is 21 days), approximately 4 months from start of neoadjuvant therapy.
Objective response rate (ORR)
ORR is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) per RECIST version 1.1, as assessed by the investigator.
Time frame: From start of neoadjuvant therapy until definitive surgery, assessed every 2 cycles (each cycle is 21 days) during neoadjuvant treatment.
EFS
Event-free survival (EFS) is defined as the time from the first neoadjuvant treatment to the first occurrence of any of the following events: (1) disease progression during neoadjuvant therapy (locoregional progression or distant metastasis) precluding radical surgery; (2) locoregional recurrence or distant metastasis after definitive surgery; (3) second primary malignancy; or (4) death from any cause.
Time frame: From date of first neoadjuvant treatment until the date of first documented event, assessed up to 5 years.
iDFS
Invasive disease-free survival (iDFS) is defined as the time from the first neoadjuvant treatment to invasive disease recurrence (including local recurrence, ipsilateral and contralateral invasive breast cancer, distant recurrence), new primary tumor, or death from any cause.
Time frame: From date of first neoadjuvant treatment until the date of first documented invasive disease recurrence or death, assessed up to 5 years.
OS
Overall survival (OS) is defined as the time from the first neoadjuvant treatment to death from any cause.
Time frame: From date of first neoadjuvant treatment until the date of death from any cause, assessed up to 5 years.
Safety and tolerability
Incidence, severity, and type of treatment-related adverse events (AEs) and serious adverse events (SAEs), graded according to NCI CTCAE version 5.0.
Time frame: From signing of informed consent through 30 days after the last dose of study treatment, assessed up to 5 years.
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