UK multicentre real-world data of the use of cyclin-dependent kinase 4/6 inhibitors in metastatic breast cancer
Bibliographic record
Abstract
Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) are widely used to treat hormone receptor-positive (HR+)/ human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). This study aimed to capture the real-world efficacy and tolerability of CDK 4/6is. Patients and methods: Data were retrospectively collected from five centres in South West England between April 2017 and November 2022. Results: Six hundred and sixty-six patients were included (median age 66 years; interquartile range 23-92 years). Five hundred and forty-four (82.7%) were treated with CDK4/6i as first-line therapy and 122 (18.3%) as second-line therapy. Median follow-up time was 28 months (range 0-76 months). Five hundred and thirty-seven received palbociclib (80.6%), 85 patients received abemaciclib (12.8%) and 44 received ribociclib (6.6%). Palbociclib and ribociclib most frequently caused neutropenia (38.2% and 26.4%, respectively) whilst abemaciclib caused diarrhoea (61.2%). Rates of dose reduction (DR) (between 53.8% and 59.2%) and time to first DR were similar for all agents (2-3 cycles). For first-line therapy, median progression-free survival (PFS) was 31 months (25-35 months) for palbociclib, 16 months [9 months-not reached (NR)] for abemaciclib and 44 months (21-NR) for ribociclib. Median overall survival (OS) was 47 months (41 months-NR) for palbociclib and was not reached for abemaciclib or ribociclib. Low patient numbers precluded analysis of second-line therapy. On multivariate analysis, visceral metastases and Eastern Cooperative Oncology Group performance status were associated with shorter PFS and OS, whilst DR was associated with longer PFS and OS. Conclusion: These data demonstrate that CDK4/6is are an effective and safe treatment for metastatic HR+/HER2- breast cancer. Efficacy was in line with trial data and other real-world data. DR was associated with improved PFS and OS, suggesting that trials of CDK4/6is at a lower starting dose are warranted.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.011 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.004 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".