Anlotinib plus chemotherapy as neoadjuvant treatment of high-risk, early-stage triple-negative breast cancer: A prospective, single-arm, single-center, phase II clinical study.

e12585 Background: 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 triple-negative breast cancer (TNBC). This phase II study aims to evaluate the efficacy and safety of adding anlotinib to standard neoadjuvant chemotherapy in primary TNBC. Methods: Patients aged 18 years or older with previously untreated stage ⅡB-IIIA histologically documented TNBC were assigned to receive chemotherapy plus oral Anlotinib (12 mg qd, d1-14; 21 days per cycle; total 8 cycles). Chemotherapy comprised of epirubicin at 90 mg/m2 and cyclophosphamide at 600 mg/m2 followed by docetaxel at 100 mg/m2, (21 days per cycle; both total 4 cycles), which was then followed by surgery. The primary endpoint was pathologic complete response (pCR) (no invasive carcinoma in breast or axilla). Stratification was based on the clinical breast cancer stage. This study is registered on Chinese Clinical Trials.gov (ChiCTR2000038174), and still ongoing. Results: Between July 2019 to June 2020, 18 patients (female) with pathological stage ⅡB (83.3%), and IIIA (16.7%) were enrolled with a median age of 46 years (range: 32-72). Overall pCR rate was 44.4% (8/18, CI 95%: 24.6%-66.3%). The pCR rate of pathological stage IIB patients was 46.7%(CI 95%: 26.7%-69.9%), which is tend to be better than the pCR rate of 33.3%(CI 95%: 6.2%-79.2%) for patients with pathological stage IIIA. There are 21 kind of AEs were observed, all including 56 times grade 1 AEs and 34 times grade 2 AEs, no grade 3 or higher AE was observed. The most common AEs included hand-foot syndrome(55.6% in total with 33.3% grade 2 and 22.2% grade 1), oral mucositis(50.00% in total with 33.3% grade 2 and 16.67% grade 1), fatigue(61.1%, all grade 1), hoarse voice(33.3%, all grade 1), nasal bleeding(27.8%, all grade 1), hypertension(22.2% with 5.6% grade 2) and diarrhea(22.2% with 5.6% grade 2). Neither unexpected safety signals nor treatment-related death occurred. Conclusions: The addition of anlotinib to neoadjuvant chemotherapy showed manageable toxicity and promising antitumor activity for patients with high-risk, early-stage TNBC. Clinical trial information: ChiCTR2000038174.