450P - A prospective, single-arm, single-center, exploratory clinical study of anlotinib combined with irinotecan in second-line and above treatment of HER-2-negative advanced breast cancer

Background

The group of HER2-negative accounts for 70-80% of breast cancer and effective treatments for heavily pretreated patients with HER2-negative metastatic breast cancer are urgently needed. Irinotecan is a semi-synthetic water-soluble camptothecin derivative which can be used as a chemotherapeutic agent for HER2-negative breast cancer after failure of anthracycline and taxanes treatments. Anlotinib is a novel multitarget tyrosine kinase inhibitor targeting VEGFR, PDGFR, FGFR, and c-Kit. This study aimed to evaluate the efficacy and safety of irinotecan combined with anlotinib in second-line and above treatment of HER-2-negative advanced breast cancer.

Methods

This open-label, single-arm, phase II study enrolled women ≥ 18 years with HER2-negative breast cancer who underwent ≥1 line chemotherapy, All patients were treated with intravenous irinotecan (60mg/m² on days 1 and 8) and oral anlotinib (12 mg once daily on days 1-14). The combination regimen repeated every 21 days. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), disease control rate (DCR), overall survival (OS) and safety.

Results

From November 2020 to April 2023, 20 patients were enrolled in this study. Median follow-up was 10.8 months (95% CI 0-21.8). Median PFS was 4.8 months (95% CI 3.0-6.6). Of all the patients whose efficacy could be evaluated (15/20), no patient achieved complete response (CR); 4(26.7%) and 9(60%) patients got partial response (PR) and stable disease (SD), respectively. ORR was 26.7% (95% CI 7.8-55.1) and DCR was 86.7% (95% CI 59.5-98.3). OS has not reached. The major treatment-related adverse events were hypertension (30%), fatigue (25%), neutropenia(20%), hand foot syndrome (15%) and myelosuppression (10%). There was one case of grade 3 nausea, and no grade 3/4 adverse events occurred . 20% (4/20) of patients had dose reductions.

Conclusions

The combination of irinotecan and anlotinib showed better treatment response and tolerable toxicity in the treatment of second-line and above patients with HER2-negative metastatic breast cancer. Further studies enrolling more patients are still needed.

Clinical trial identification

ChiCTR2000037448.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.