Studies have indicated that the improvement in pathological complete response (pCR) is significantly correlated with triple-negative breast cancer(TNBC)patients' overall survival (OS). Patients with TNBC have poor efficacy for neoadjuvant chemotherapy. The combination of neoadjuvant therapy with immunotherapy and chemotherapy has been demonstrated to enhance the pCR rate of TNBC patients, increasing it from 45% to approximately 60%. Therefore, how to further improve the pCR rate of TNBC breast cancer became the main objective of this study. Stereotactic radiotherapy (SBRT) not only kills tumor cells directly, but also kills the distant unirradiated tumor cells by promoting the cross-initiation of tumor-specific CD8+ T cells, a phenomenon known as the abscopal effect. Our research team has recently discovered that the triple therapy model of SBRT + anti-vascular targeting + anti-PD-1 was safe and efficacious in lung cancer patients. Cadonilimab (AK104) is an PD-1/CTLA-4 bispecific antibody. In order to improve the pCR, a single-arm, open, phase II clinical study was proposed to explore the safety and efficacy of SBRT+AK104+chemotherapy, a neoadjuvant treatment modality, in the treatment of TNBC.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
51
8Gy\*3 SBRT to irradiate the primary lesion (without axillary lymph node metastasis) or 6Gy\*3 SBRT irradiation to irradiate the primary lesion and axillary lymph node metastasis will be administered at first. And then the first cycle of chemotherapy+AK104 given within 24 hours of the end of SBRT. The total eight cycles of preoperative chemotherapy combined with immunotherapy were administered. Surgical resection was performed within 4-6 weeks after the completion of the eighth cycle of chemotherapy combined with immunotherapy. The chemotherapy regimen consisted of: Four cycles of doxorubicin 50mg/m2 (Q3W) + cyclophosphamide 600mg/m2 (Q3W) were administered, followed by four cycles of sequential albumin paclitaxel (125 mg/m2, d1, d8) and carboplatin (AUC=6, d1, Q3W) for 4 cycles. Postoperative completion of 9 cycles of immunotherapy was continued ± the need for postoperative adjuvant radiotherapy was confirmed based on the patient's preoperative status.
Hubei Cancer Hospital
Wuhan, Hubei, China
RECRUITINGComplete pathologic remission (pCR) rate
pCR is defined as ypT0/Tis and ypN0
Time frame: Up to the 30 weeks
Objective response rate
Defined as percentage of participants achieving assessed complete response (CR) and partial response (PR) by the investigator according to the RECIST 1.1.
Time frame: Up to the 30 weeks
EFS
Event free survival
Time frame: Up to 12 months after surgery
Quality of life assessment
Using the EORTC QLQ-BR2. It is based on the core cancer scale EORTCQLQ1-C30 with 23 additional scales specific to breast cancer patients. The questions are specified in the QLQ1C30, and by summing all the questions, a score (0-100) is obtained that is positively related to the quality of life of breast cancer patients.
Time frame: Up to 12 months after surgery
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