Anlotinib combined with neoadjuvant chemotherapy for HR+/HER2- breast cancer (ACNTBC): a prospective, single-arm, single-center phase II clinical study with real-world validation.

Despite being an option for high-risk or inoperable cases, existing neoadjuvant therapies for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer yield suboptimal pathological responses, necessitating novel strategies. This prospective, phase II ACNTBC trial (NCT05558722) investigated the efficacy and safety of combining anlotinib with chemotherapy as a neoadjuvant treatment for HR+/HER2- breast cancer. Enrolled patients received 5 cycles of anlotinib (12 mg qd, d1‒14; q3w) plus 6 cycles of nab-paclitaxel (200 mg/m2, q3w), pirarubicin (50 mg/m2, q3w), and cyclophosphamide (500 mg/m2, q3w). The primary endpoint was the total pathological complete response (tpCR) rate, with the major secondary endpoints including residual cancer burden (RCB) 0/I rate, objective response rate (ORR), and safety. The study enrolled 31 patients, and the ORR was 93.5% (29/31, 95% CI, 78.6-99.2). In the per-protocol set of 28 patients completing treatment and surgery, the tpCR rate was 14.3% (4/28, 95% CI, 4.0-32.7), with RCB 0/I rate of 25.0% (7/28, 95% CI, 10.7-44.9). Grade 3/4 adverse events included hematologic toxicities, hypertension, proteinuria, and headache, all manageable. Post-hoc biomarker analysis showed that high baseline VEGFR2 expression and microvessel density (MVD) were significantly associated with superior efficacy, and the treatment significantly reduced Ki-67 index, VEGFR2 expression, and MVD. Supporting evidence from an exploratory inverse probability of treatment weighting (IPTW) analysis using a real-world cohort receiving chemotherapy alone indicated a potential benefit of the combination over chemotherapy alone. In conclusion, neoadjuvant anlotinib plus chemotherapy demonstrates promising efficacy and manageable safety in HR+/HER2- breast cancer with a high Ki-67 index.