246P - Phase II study of anlotinib combined with taxanes and lobaplatin in the neoadjuvant treatment of triple-negative breast cancer: Efficacy, safety and biomarker analysis from the neoALTAL trial

Background

Anlotinib, a novel multi-target tyrosine kinase inhibitor, has been proven effective in HER2-negative metastatic breast cancer, but its efficacy in early-stage TNBC is unknown. This phase 2 study aims to evaluate the efficacy and safety of adding anlotinib to neoadjuvant chemotherapy (NCT) in patients (pts) with TNBC.

Methods

Pts with clinical stage II/III TNBC were treated with 5 cycles of anlotinib (12mg, d1-14, q3w) plus 6 cycles of taxanes (docetaxel 75 mg/m² or nab-paclitaxel 125 mg/m², d1 and d8, q3w) and lobaplatin (30 mg/m², d1, q3w), followed by surgery. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0) and the secondary endpoints include breast pCR (bpCR), axillary pCR (apCR), survival, and safety. Exploratory endpoints were efficacy biomarkers based on FUSCC classification (IHC-based) and NGS (425 gene panel).

Results

From Jan 2021 to Aug 2022, 48 pts were assessed and 45 were enrolled. All pts received at least one dose of study treatment and underwent surgery. The median age was 50 years (range, 26-65), 71% were nodal involved, and 20% had stage III. In the ITT population, 26 out of 45 pts achieved tpCR (57.8%; 95% CI, 42.2%–72.3%), and 39 achieved RCB 0-I (86.7%; 95% CI, 73.2%-94.9%). The bpCR and apCR rates were 64.4% (29/45) and 71.9% (23/32), respectively. No recurrence or metastasis occurred during the short-term follow-up. Based on the FUSCC IHC-based subtypes, the tpCR rates were 68.8% (11/16) for IM subtype, 58.3% (7/12) for BLIS subtype, and 33.3% (4/12) for LAR subtype, respectively. Next-generation sequencing revealed that the tpCR were 69.2% (9/13) and 53.6% (15/28) in MYC-amplified and wild-type pts, respectively, and 75.0% (9/12) and 51.7% (15/29) in BRCA1/2-mutated and wild-type pts, respectively. In the safety population (N=45), Grade 3 or 4 TEAEs occurred in 29 pts (64%), and the most common events were neutropenia (38%), leukopenia (27%), thrombocytopenia (25%), anemia (13%), and hypertension (13%), respectively. No treatment-related deaths occurred.

Conclusions

The addition of anlotinib to NCT showed manageable toxicity and promising antitumor activity for pts with early-stage TNBC.

Clinical trial identification

ChiCTR2100043027.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Chia Tai Tianqing Pharmaceutical Group Co., Ltd. L.

Disclosure

All authors have declared no conflicts of interest.