The efficacy and safety of apatinib combined with paclitaxel and carboplatin dose-dense regimen in neoadjuvant therapy for locally advanced triple-negative breast cancer.

Abstract

e12602 Background: Triple negative breast cancer (TNBC) has the traits of early onset, high malignancy and no effective molecular targets to act on, neoadjuvant chemotherapy is recommended as the preferred treatment for locally advanced TNBC with highly recurrence risk. The addition of platinum-based agents to conventional taxanes regimens in locally advanced TNBC can significantly improve pathological complete response (pCR) rate. Anti-angiogenic drugs are currently one of the few targeted therapies that have achieved efficacy in TNBC. Apatinib, an inhibitor of VEGFR2, shows significant antitumor activity in the patients with breast cancer. Methods: Pathologically confirmed TNBC patients with clinical stage I-IIIC (per AJCC 8th ed) with no previous surgery or radio-chemotherapy treatment were enrolled in our center from September 2018 to June 2020. Enrolled patients received 4-8 neoadjuvant treatment cycles of apatinib 250mg per day + paclitaxel 175mg/m2 d1 + carboplatin AUC = 4 d2 q14d (Apa+TC), followed by sequential surgery. Enrolled patients who underwent surgery were matched with TNBC patients received paclitaxel and carboplatin intense regimen (TC) contemporarily in our center by propensity score matching (PSM). pCR in breast and axilla (ie. ypT0/Tis ypN0) was the primary endpoint. Objective response rate (ORR), disease control rate (DCR), event-free survival (EFS), overall survival (OS) and adverse events (AEs) are secondary endpoints. Results: 25 locally advanced TNBC patients were enrolled for neoadjuvant therapy of Apa+TC. In radiological evaluation, 2 patients achieved CR, 20 patients achieved PR, 3 patients achieved SD, which indicated an ORR of 88% and a DCR of 100%. 23 of 25 enrolled patients underwent surgery, with a pCR rate of 60.87% (95%CI: 38.54%-80.29%). 69 patients who were treated by TC before surgery were matched by PSM based on baseline stage T and stage N features. A significant higher pCR rate was achieved in Apa+TC arm compared with TC alone (60.87% vs. 30.43%, respectively, P = 0.009). Similar incidence of AEs was observed between two arms. The main AEs were hematologic toxicities fatigue, digestive canal symptoms, transaminase elevation and peripheral neurotoxicity in Apa+TC arm. Grade III-IV AEs included granulocytopia (14/25), thrombocytopenia (4/25), anaemia (3/25), fatigue (1/25), hypertension (1/25) and arrhythmia (1/25). Meanwhile, apatinib-related AEs, including hypertension, proteinuria, and hand-and-foot syndrome, were mild. Due to the limited time, the survival follow-up is still in progress. Conclusions: Apatinib combined with paclitaxel and carboplatin intensive regimen achieved a better efficacy and manageable adverse events in neoadjuvant chemotherapy for locally advanced TNBC, which might be a promising strategy in the treatment of locally advanced TNBC. Clinical trial information: NCT03735082.

WITHDRAWN: New Breakthrough in Triple-Negative Breast Cancer Treatment: A Study on the Clinical Efficacy and Safety of the Combination of Carrilizumab and Apatinib in Dual-Targeted Neoadjuvant Therapy

“…In recent years, with improvements in living standards, changes in dietary habits, and advancements in medical care, the incidence of breast cancer has been steadily increasing, making it the most prevalent cancer among women. Triple-negative breast cancer (TNBC) [1][2][3][4] , characterized by its propensity for recurrence, metastasis, high malignancy, and unstable biological behavior, has become a focal point of interest in terms of treatment methods and prognosis. Apatinib [5][6][7] , an anti-tumor angiogenesis drug targeting the vascular endothelial growth factor receptor 2 (VEGFR2), has shown promising results in creating a hypoxic tumor microenvironment and reducing tumor burden.…”

Apatinib beyond first progression is associated with prolonged overall survival in patients with advanced breast cancer: Results from an observational study

“…Apatinib, as a VEGFR2 inhibitor, has shown moderate efficacy in the treatment of metastatic breast cancer, and is currently used as an option for maintenance salvage therapy following failure of treatment with multiple lines of treatment (8,9). Apatinib combined with dose-dense paclitaxel and carboplatin neoadjuvant therapy was previously shown to significantly improve the pathological complete response rate to 60.9% in patients with triple-negative breast cancer who underwent surgery (10). However, rebound tumor growth occurred when VEGFR tyrosine kinase inhibitor (TKI) treatment was discontinued after the acquisition of resistance, and this growth was ultimately reversed after long-term anti-angiogenic treatment withdrawal (11).…”