Chemotherapy-free survival in HR-positive HER2-negative breast cancer: CDK4/6 inhibitors combination vs. endocrine monotherapy.

e13050 Background: Treatment of hormone receptor (HR)-positive HER2-negative advanced breast cancer (ABC) with CDK4/6 inhibitors (CDK4/6i) significantly extends progression-free survival (PFS) compared to endocrine monotherapy. While reports on chemotherapy-free survival (CFS) exist in Europe and the U.S., few studies have been published in Asia. This study aims to assess the non-inferiority of CFS in HR-positive HER2-negative ABC by comparing the CDK4/6i and endocrine monotherapy groups as first-line treatments. Methods: This multi-center, retrospective observational study included patients with HR-positive HER2-negative ABC who received first-line endocrine therapy between 2015 and 2020. The characteristics of patients who chose CDK4/6i or monotherapy were examined. Additionally, CFS, PFS, and PFS2 (combined PFS for patients on first- and second-line endocrine therapy) were assessed. Patient characteristics were adjusted using inverse probability of treatment weighting (IPTW). A non-inferiority margin for CFS of 1.2 was set. Results: Of 443 cases, 125 were in the CDK4/6i group and 318 in the monotherapy group. The CDK4/6i group had a higher proportion of patients with PS 0 and organ metastasis (lung, liver), while the monotherapy group had more bone-only metastasis. After adjusting for patient background using IPTW, differences between the groups remained only based on the time of diagnosis (CDK4/6 inhibitors were approved in Japan in 2017). During a median follow-up of 36 months for the CDK4/6i group and 46 months for the monotherapy group, 298 CFS events (67%) occurred. The median CFS was 30 months for the CDK4/6i group and 35 months for the monotherapy group (HR: 0.93, 95% CI: 0.70–1.24). In patients with PS 0, no liver metastasis, de novo stage IV, or DFI ≥60 months, the median CFS for the monotherapy group was 48 months. The median PFS was 12 months for both groups, with no significant difference (HR: 1.11, 95% CI: 0.88–1.40). However, PFS2, which included patients continuing first-line treatment or received endocrine therapy in second-line treatment was 33 months for the CDK4/6i group and 28 months for the monotherapy group, with the CDK4/6i group showing a significant extension (HR: 1.41, 95% CI: 1.01–1.97). Discussion: In this limited sample study, the monotherapy group showed a slightly better trend in CFS. The CDK4/6i had more adverse events compared to the monotherapy. In Japan, where universal health insurance system exists, the out-of-pocket costs for CDK4/6i are significantly higher. In subgroups with a good prognosis, starting monotherapy as first-line treatment may result in a long CFS, making the selection of CDK4/6i as second-line treatment a viable treatment strategy. Conclusions: In HR-positive HER2-negative ABC, the monotherapy group did not show non-inferiority in CFS compared to the CDK4/6i group, with a small difference in this real-world cohort.