SynthesisBreast cancer research : BCR2026
CDK4/6 inhibitors rechallenge post-progression in HR-positive HER2-negative advanced/metastatic breast cancer patients: a meta-analysis of Kaplan-Meier-reconstructed individual-level data.
Synthesis in Breast cancer research : BCR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Authors and funding
6 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundCyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) are the standard of care for hormone receptor (HR)-positive, HER2-negative advanced/metastatic breast cancer (BC). However, the optimal strategy after progression remains uncertain.
methodsPubMed, Cochrane, and Embase databases were searched in April 2025 for phase II/III clinical trials evaluating CDK4/6i rechallenge in advanced breast cancer. We evaluated progression-free survival (PFS) and overall survival (OS) using Cox proportional hazards models, reporting hazard ratios (HRs) with 95% confidence intervals (CIs). Analyses were conducted on R (v.4.2.2).
resultsEight trials including 1396 patients were included, of whom 839 received CDK4/6i rechallenge plus ET, and 557 received ET alone. Median PFS was 5.8 months vs 3.7 months, with a 29% reduction in risk of progression or death (HR 0.71; 95% CI 0.63-0.81; P < 0.001). No OS benefit was observed (HR 1.04; 95% CI 0.70-1.55). Switching to a different CDK4/6i appears to confer greater benefit (HR 0.61; 95% CI 0.52-0.72), yet most patients who switched CDK4/6i received abemaciclib, which was associated with the longest PFS (7.9 months) compared with palbociclib (4.6 months) or ribociclib (5.5 months). Patients harboring ESR1 or PIK3CA alterations demonstrated a median PFS of 5.3 (3.6-7.4) and 4.7 (3.6-6.7) months, respectively.
conclusionsThis meta-analysis suggests that CDK4/6 inhibitor rechallenge post-progression offers additional benefit to ET alone.
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