The preliminary efficacy and safety results of neoadjuvant phase II study of anlotinib plus tislelizumab combined with chemotherapy in triple-negative breast cancer.

e12600 Background: The KEYNOTE-522 trial demonstrated that adding pembrolizumab to chemotherapy improves the pathologic complete response (pCR) rate and survival in triple-negative breast cancer (TNBC). Several studies have also shown that antiangiogenic agents can enhance the response to immune-checkpoint inhibitors. This study aims to assess the efficacy and safety of anlotinib (a multitarget anti-angiogenic TKI), tislelizumab (anti-PD-1 antibody), combined with nab-paclitaxel and anthracycline as a neoadjuvant regimen for patients with TNBC. Methods: In this prospective, single-arm, open-label, phase II trial, patients with untreated, histologically confirmed TNBC in stage II-III were enrolled. Patients received 5 cycles of anlotinib (8 mg qd, d1-14; 21 days per cycle) with 6 cycles of tislelizumab (200 mg, once every 3 weeks) plus nab-paclitaxel (260 mg/m 2 , once every 3 weeks) and anthracycline (epirubicin 75 mg/m 2 or doxorubicin 60 mg/m 2 ), followed by surgery. Adjuvant chemotherapy and immunotherapy were at the discretion of the treating physician, and radiation therapy was per standard of care. The primary endpoint is the pCR (ypT0/Tis ypN0) rate, and the secondary endpoints include invasive disease-free survival (iDFS), event-free survival (EFS), overall survival (OS), adverse events (AE), and immune response biomarkers. Results: From Nov 2023 to Dec 2024, 19 patients were received neoadjuvant treatment and underwent breast surgery. The median age was 45 years (range, 30-68). At diagnosis, 16 (84.2%) patients were clinical stage II, 9/19 (47.4%) were clinically node positive. 13 of the 19 patients achieved pCR (68.4%; 95% CI, 46%-84.6%). The ORR and DCR were 47.4% (95% CI, 27.3%-68.3%) and 100% (95%CI, 85.7%-100%), respectively. Subgroup analysis showed the pCR rate of patients who were diagnosed initially to be lymph node positive was 77.7% (7/9), higher than that of patients who were lymph node negative (60%; 6/10). By the clinical stage, the pCR rate was 62.5% (10/16) in patients with stage II, and 100% (3/3) in those with stage III. Treatment-emergent adverse events (TEAEs) of any grade occurred in all 19 pts, with 15 (78.9%) experiencing grade ≥3 TEAEs. The most common grade ≥3 TEAEs were leukopenia (78.9%), neutropenia (73.7%), increased GGT (10.5%), and anemia (5.3%). Conclusions: The preliminary results demonstrated that anlotinib plus tislelizumab and chemotherapy as neoadjuvant therapy for TNBC showed promising antitumor efficacy and manageable safety profile. The study is still ongoing. Clinical trial information: NCT04914390 .