Sequential CDK4/6 Inhibitor Therapy Versus mTOR Inhibitor Therapy Following Initial CDK4/6 Inhibitor in HR+/HER2- Advanced Breast Cancer
Author(s)
Munenobu Kashiwa, PhD1, Kosuke MORIMOTO, MS2, Kensuke Moriwaki, BS, MS, PhD2.
1Ritsumeikan University, Research Organization of Science and Technology Comprehensive Unit for Health Economic Evidence Review and Decision Support (CHEERS), Kyoto City, Japan, 2Ritsumeikan University, Research Organization of Science and Technology Comprehensive Unit for Health Economic Evidence Review and Decision Support (CHEERS), Kyoto city, Japan.
1Ritsumeikan University, Research Organization of Science and Technology Comprehensive Unit for Health Economic Evidence Review and Decision Support (CHEERS), Kyoto City, Japan, 2Ritsumeikan University, Research Organization of Science and Technology Comprehensive Unit for Health Economic Evidence Review and Decision Support (CHEERS), Kyoto city, Japan.
OBJECTIVES: To compare overall survival (OS) between sequential CDK4/6 inhibitor therapy and mTOR inhibitor therapy in HR+/HER2- advanced breast cancer patients treated with first-line CDK4/6 inhibitors, and to evaluate the impact of short-term (0-24-month) hazard ratios on long-term survival prediction via time-dependent analysis.
METHODS: This retrospective cohort study used a Japanese health insurance claims database (2018-2024) to identify HR+/HER2- advanced breast cancer patients who received first-line CDK4/6 inhibitors. Patients then received either an alternative CDK4/6 inhibitor (sequential group, n=261) or exemestane plus everolimus (mTOR group, n=191) as second-line treatment. Primary endpoints were OS from first-line and second-line initiation. Survival outcomes were estimated using Kaplan-Meier methods and compared using Cox proportional hazards models. Additionally, the data were segmented into observation intervals (0-24 months and ≥36 months) to assess the time dependency of hazard ratios and the implications for long-term extrapolation based on short-term trial data.
RESULTS: OS from first-line initiation showed no significant difference between the groups (HR=0.92, 95% CI: 0.62-1.36, p=0.670), with 48-month survival rates of 64.9% and 64.2% for the sequential and mTOR groups, respectively. Similarly, OS from second-line initiation did not significantly differ (HR=1.33, 95% CI: 0.89-1.97, p=0.160). Treatment duration analysis revealed that the sequential group experienced a longer first-line duration (median: 11 vs 9 months, p=0.002), comparable second-line duration (median: 4 months, p=0.573), and that the mTOR group had a longer third-line duration (median: 12 vs 9 months, p=0.001). Time-dependent analysis indicated a hazard ratio of 0.76 (95% CI: 0.44-1.32, p=0.328) during 0-24 months compared with 1.15 (95% CI: 0.53-2.50, p=0.715) beyond 36 months.
CONCLUSIONS: Both sequential CDK4/6 inhibitor and mTOR inhibitor therapies yield comparable OS in HR+/HER2- advanced breast cancer, despite different treatment durations. The time-dependent variability in hazard ratios cautions against directly extrapolating short-term data for long-term predictions, highlighting the need for prospective validation.
METHODS: This retrospective cohort study used a Japanese health insurance claims database (2018-2024) to identify HR+/HER2- advanced breast cancer patients who received first-line CDK4/6 inhibitors. Patients then received either an alternative CDK4/6 inhibitor (sequential group, n=261) or exemestane plus everolimus (mTOR group, n=191) as second-line treatment. Primary endpoints were OS from first-line and second-line initiation. Survival outcomes were estimated using Kaplan-Meier methods and compared using Cox proportional hazards models. Additionally, the data were segmented into observation intervals (0-24 months and ≥36 months) to assess the time dependency of hazard ratios and the implications for long-term extrapolation based on short-term trial data.
RESULTS: OS from first-line initiation showed no significant difference between the groups (HR=0.92, 95% CI: 0.62-1.36, p=0.670), with 48-month survival rates of 64.9% and 64.2% for the sequential and mTOR groups, respectively. Similarly, OS from second-line initiation did not significantly differ (HR=1.33, 95% CI: 0.89-1.97, p=0.160). Treatment duration analysis revealed that the sequential group experienced a longer first-line duration (median: 11 vs 9 months, p=0.002), comparable second-line duration (median: 4 months, p=0.573), and that the mTOR group had a longer third-line duration (median: 12 vs 9 months, p=0.001). Time-dependent analysis indicated a hazard ratio of 0.76 (95% CI: 0.44-1.32, p=0.328) during 0-24 months compared with 1.15 (95% CI: 0.53-2.50, p=0.715) beyond 36 months.
CONCLUSIONS: Both sequential CDK4/6 inhibitor and mTOR inhibitor therapies yield comparable OS in HR+/HER2- advanced breast cancer, despite different treatment durations. The time-dependent variability in hazard ratios cautions against directly extrapolating short-term data for long-term predictions, highlighting the need for prospective validation.
Conference/Value in Health Info
2025-09, ISPOR Real-World Evidence Summit 2025, Tokyo, Japan
Value in Health Regional, Volume 49S (September 2025)
Code
RWD271
Topic Subcategory
Health & Insurance Records Systems
Disease
SDC: Oncology