A new option for post-CDK4/6is resistance era? Multicenter real-world study of anlotinib-based combination therapy in hormone receptor-positive metastatic breast cancer resistant to CDK4/6 inhibitors.

e13059 Background: Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors (CDK4/6is) combined with hormonal therapy are the current standard frontline treatment for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER-2)-negative metastatic breast cancer (MBC). However, the optimal treatment after progression on CDK4/6is remains unknown. Anlotinib is an oral multi-target tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. This study aimed to evaluate the safety and efficacy of anlotinib-based combination therapy in patients with HR+ MBC previously treated with CDK4/6is. Methods: 71 patients from 8 medical centers with pathologically confirmed HR-positive, HER-2-negative MBC were retrospectively reviewed. All included patients had received at least one line of CDK4/6is therapy before disease progression prior to anlotinib-based combination therapy. Anlotinib (12 mg daily, Day 1-14 of each cycle) was administered orally to fasting patients, with dose reductions to 10 mg or 8 mg in cases of intolerable toxicity. Combination agents included eribulin, nab-paclitaxel, etoposide, capecitabine, pembrolizumab, sintilimab, or fulvestrant, among others. Hospital medical records and imaging systems were used to assess clinical characteristics. The primary endpoint was progression free survival (PFS) and secondary endpoints were objective response rate (ORR), disease control rate (DCR), and overall survival. The safety profile has also been assessed. Results: Between January 2020 and December 2024, 71 patients were included, with a median age of 54 years (range: 32-81 years). In the 57 patients whose efficacy could be evaluated, the median follow-up was 9.2 months (95% CI, 6.6-11.8), and the median PFS was 6.5 months (95% CI，5.48-7.54). The ORR was 28.1% (95% CI，17.0%-41.5%, and the DCR was 87.7% (95% CI, 76.3%-94.9%), with partial response and stable disease observed in 16 and 34 patients, respectively. The most common adverse events (AEs) were alanine aminotransferase elevation (23 patients, 32.4%), leukopenia (19 patients, 26.8%), and anemia (18 patients, 25.4%). It also includes widely observed AEs such as hypercholesteremia (14 patients, 19.7%), hypertension (7 patients, 9.9%), albuminuria (7 patients, 9.9%), among others. Grade 3/4 treatment-emergent AEs occurred in 12 patients (16.9%), with the most common being aspartate aminotransferase elevation (3 patients, 4.2%). Dose reductions of anlotinib were required in 6 patients (8.5%). Conclusions: Anlotinib-based combination therapy has demonstrated good efficacy and acceptable safety in HR+/HER2- MBC patients previously treated with CDK4/6is, making it a viable treatment option following resistance to CDK4/6is. Clinical trial information: NCT06734533 .