The efficacy and safety of apatinib combined with paclitaxel and carboplatin dose-dense regimen in neoadjuvant therapy for locally advanced triple-negative breast cancer.
Authors: Li Qiao , Liu Jiaxuan , Zhang Pin , Ma Fei , Luo Yang , Yuan Peng , Wang Jiayu , Ou Kaiping , Wang Xin , Qi Liqiang , Wang Yipeng , He Maiyue , Lv Jianhong , Yang Yang , Xu Binghe 
Published: June 2022

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.