First-Line Treatment Sequencing Associated With an Improved Progression-Free Survival in Patients With Metastatic Breast Cancer

Estrogen-receptor positive (ER+) and human epidermal growth factor 2-negative (HER2–) breast cancer compromises over 70% of all breast cancer cases.¹ Current first-line standard of care therapy for this breast cancer subtype is cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy as up to 20% of patients have an innate resistance to endocrine therapy while, for other patients, resistance is acquired over time.¹ The combined therapy has been found to suppress cell proliferation, delay the progression of cancer, and has be demonstrated to improved overall survival for patients.¹ CDK4/6i inhibit retinoblastoma protein phosphorylation which leads to G1 cell-cycle arrest of tumor cells and stops cancer cell proliferation.¹

To further understand the benefit of CDK4/6i combined with endocrine therapy as first- or second-line treatment for patients with HR+/HER2 metastatic breast cancer, a retrospective analysis was performed. The study used nationwide data available via electronic health records to estimate the real-world progression-free survival (rwPFS) and overall survival (rwOS) of 2771 patients with metastatic breast cancer. The patients in the study had ≥3 months of follow-up. First-line treatment with a CDK4/6i combined with endocrine therapy was received by 2170 patients. The second group of 601 patients received endocrine therapy in the first-line setting and CDK4/6i plus endocrine therapy in the second-line setting. To test for an association of CDK4/6i treatment line sequence on PFS and OS, the Kaplan-Meier method and Cox proportional hazards were used.

For patients receiving CDK4/6i plus endocrine therapy as first-line treatment the time to chemotherapy from start of first-line therapy median follow-up was 67.6 months. The median follow-up for patients receiving endocrine therapy alone first-line and CDK4/6i combined with endocrine therapy as second-line treatment time to chemotherapy from the start of first-line therapy was 41.0 months. Data analysis found that first-line treatment of CDK4/6i combined with endocrine therapy had a rwPFS of 49.0 months from time to third-line therapy from first-line therapy. The median rwOS was 54 months for this group. The rwPFS for patients receiving endocrine therapy alone first-line followed by CDK4/6i combined with endocrine therapy second-line was 22.0. months from time to third-line therapy from first-line therapy. The median rwOS for this treatment group was 49 months. Similar results were found after a propensity scores matching analysis was performed.

Kimmick G, Pilehvari A, Wen Y, Bonilla G, Anderson R. The impact of treatment sequence of CDK4/6 inhibitor therapy on metastatic breast cancer treatment outcomes in real-world practice in the U.S. Poster presented at: San Antonio Breast Cancer Symposium. December 6, 2023; San Antonio, TX. Abstract #PO1-17-12.

Reference:

1. Zhou FH, Downton T, Freelander A, et al CDK4/6 inhibitor resistance in estrogen receptor positive breast cancer, a 2023 perspective. Front Cell Dev Biol. 2023;11:1148792.