CDK4/6 inhibitors versus weekly paclitaxel for treatment of ER+/HER2- advanced breast cancer with impending or established visceral crisis.

PURPOSE: ER+/HER2- advanced breast cancer (ABC) with visceral crisis (VC) or impending VC (IVC) is commonly treated with chemotherapy instead of CDK4/6 inhibitors (CDK4/6i). However, there is little evidence to confirm which treatment is superior. This study compared outcomes of patients with ER+/HER2- ABC and IVC/VC treated with CDK4/6i or weekly paclitaxel. METHODS: Patients with ER+/HER2- ABC receiving first line treatment at a large tertiary UK cancer centre from 1-Mar-2017 to 30-Jun-2021 were retrospectively identified. Hospital records were screened for IVC/VC affecting the liver, lungs/mediastinum, gastrointestinal tract and/or bone marrow. Baseline demographics, clinical data and survival outcomes were recorded up to 30-Jul-2022. RESULTS: 27/396 (6.8%) patients with ABC who received CDK4/6i and 32/86 (37.2%) who received paclitaxel had IVC/VC. Median time to treatment failure (TTF), progression-free survival (PFS) and overall survival (OS) were significantly longer in the CDK4/6i compared to paclitaxel cohort: TTF 17.3 vs. 3.5 months (HR 0.33, 95%CI 0.17-0.61, p = 0.0002), PFS 17.8 vs. 4.5 months (HR 0.38, 95%CI 0.21-0.67, p = 0.002), OS 24.6 vs. 6.7 months (HR 0.37, 95%CI 0.20-0.68, p = 0.002). The median time to first improvement in IVC/VC was similar in patients receiving CDK4/6i compared to paclitaxel (3.9 vs. 3.6 weeks, p = 0.773). Disease control at 4 months was not significantly different in the CDK4/6i and paclitaxel cohorts (77.8% vs. 59.4%, p = 0.168). In multivariate analysis, treatment with CDK4/6i was independently associated with a longer PFS compared to paclitaxel (HR 0.31, 95%CI 0.12-0.78, p = 0.015). CONCLUSION: In this retrospective study, patients with ER+/HER2- ABC and IVC/VC treated with CDK4/6i had a significantly better survival compared to those treated with weekly paclitaxel. Further prospective studies that minimise possible selection bias are recommended.