Real-world effectiveness of CDK4/6i in first-line treatment of HR+/HER2− advanced/metastatic breast cancer: updated systematic review
Bibliographic record
Abstract
Aim: Since 2021, additional real-world evidence (RWE) has emerged on the effectiveness of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) as first-line treatment of HR-positive/HER2-negative (HR+/HER2-) advanced/metastatic breast cancer (A/MBC), necessitating this updated review. Methods: , and Cochrane Databases (07/06/2019-01/09/2024), and key congresses (2020-2024) were searched. Studies reporting first-line CDK4/6i use, over 100 participants, and progression-free survival (PFS) and/or overall survival (OS) data were included. Results: This update included 82 unique studies, 42.7% for palbociclib, 7.3% for ribociclib, and 3.7% for abemaciclib; 46.3% assessed multiple CDK4/6i. In studies including multiple CDK4/6is, median PFS was 23.4-31.0 months for palbociclib, 19.8-44.0 for ribociclib, and 14.0-39.5 for abemaciclib. When reached, median OS was 38.0-58.0 months, 40.4-52.0 months, and 34.4 months, respectively. These real-world PFS and OS results were within the range of single-arm and CDK4/6i versus endocrine therapy (ET) studies, where CDK4/6i demonstrated greater benefits than ET alone. Conclusion: First-line CDK4/6i RWE demonstrates significant clinical benefits in HR+/HER2- A/MBC. These data are important to guide clinical decision-making, as they include patients who are not adequately represented in clinical trials. Studies with longer follow-up are needed to assess long-term benefits of all three CDK4/6i therapies in HR+/HER2- A/MBC.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.015 | 0.001 |
| Bibliometrics | 0.001 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".