CDK4/6-Inhibitors Versus Chemotherapy in Advanced HR+/HER2-Negative Breast Cancer: Results and Correlative Biomarker Analyses of the KENDO Randomized Phase II Trial
Bibliographic record
Abstract
BACKGROUND: The optimal treatment approach for hormone receptor-positive/HER2-negative metastatic breast cancer (HR+/HER2-negative MBC) with aggressive characteristics remains controversial, with lack of randomized trials comparing cyclin-dependent kinase (CDK)4/6-inhibitors (CDK4/6i) + endocrine therapy (ET) with chemotherapy + ET. MATERIALS AND METHODS: We conducted an open-label randomized phase II trial (NCT03227328) to investigate whether chemotherapy + ET is superior to CDK4/6i + ET for HR+/HER2-negative MBC with aggressive features. PAM50 intrinsic subtypes (IS), immunological features, and gene expression were assessed on baseline samples. RESULTS: Among 49 randomized patients (median follow-up: 35.2 months), median progression-free survival (mPFS) with chemotherapy + ET (11.2 months, 95% confidence interval [CI]: 7.7-15.4) was numerically shorter than mPFS (19.9 months, 95% CI: 9.0-30.6) with CDK4/6i + ET (hazard ratio: 1.41, 95% CI: 0.75-2.64). Basal-like tumors under CDK4/6i + ET exhibited worse PFS (mPFS: 11.4 months, 95% CI: 3.00-not reached [NR]) and overall survival (OS; mOS: 18.8 months, 95% CI: 18.8-NR) compared to other subtypes (mPFS: 20.7 months, 95% CI: 9.00-33.4; mOS: NR, 95% CI: 24.4-NR). In the chemotherapy arm, luminal A tumors showed poorer PFS (mPFS: 5.1 months, 95% CI: 2.7-NR) than other IS (mPFS: 13.2 months, 95% CI: 10.6-28.1). Genes/pathways involved in BC cell survival and proliferation were associated with worse outcomes, as opposite to most immune-related genes/signatures, especially in the CDK4/6i arm. CD24 was the only gene significantly associated with worse PFS in both arms. Tertiary lymphoid structures and higher tumor-infiltrating lymphocytes also showed favorable survival trends in the CDK4/6i arm. CONCLUSIONS: The KENDO trial, although closed prematurely, adds further evidence supporting CDK4/6i + ET use in aggressive HR+/HER2-negative MBC instead of chemotherapy. PAM50 IS, genomic, and immunological features are promising biomarkers to personalize therapeutic choices.
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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 | 0.005 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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 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".