A Systematic Literature Review of the Effectiveness of CDK 4/6 Inhibitors for First-Line Treatment of HR+/HER2− Advanced/Metastatic Breast Cancer: A Comparison of Real-World Evidence.
Simple Summary: Drugs known as cyclin-dependent kinase 4/6 inhibitors are commonly used together with hormone therapy as the first treatment for people with hormone receptor-positive, HER2-negative advanced breast cancer. However, these drugs have not been directly compared in large clinical trials....
| Published in: | Cancers Vol. 18; no. 14; pp. 2362 - 2385 |
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| Main Authors: | , , , , , , , , , |
| Format: | research systematic review tables/charts Journal Article |
| Published: |
MDPI
Jul2026
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=195807652&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 195807652 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 20726694 B74B jtl: Cancers issn: 20726694 maglogo: N pubinfo: dt: Jul2026 vid: 18 iid: 14 pid: 97109 pub: MDPI artinfo: ui: 195807652 195807652 195807652 10.3390/cancers18142362 195807652 ppf: 2362 ppct: 23 formats: tig: atl: A Systematic Literature Review of the Effectiveness of CDK 4/6 Inhibitors for First-Line Treatment of HR+/HER2− Advanced/Metastatic Breast Cancer: A Comparison of Real-World Evidence. aug: au: Pluard, Timothy Grinda, Thomas Dienstmann, Rodrigo Thill, Marc Korytowsky, Beata Chen, Connie Portuhay, Sofiya Salvo-Halloran, Elizabeth M. Samjoo, Imtiaz A. Harbeck, Nadia affil: Hematology and Medical Oncology, St. Luke's Cancer Institute, Kansas City, MO 64111, USA sug: subj: Breast Neoplasms Drug Therapy Neoplasm Metastasis Drug Therapy Cyclin-Dependent Kinases Therapeutic Use Antineoplastic Agents, Combined Treatment Outcomes Funding Source Human Systematic Review Descriptive Statistics Medline Embase Cochrane Library Gray Literature Progression-Free Survival Checklists Confidence Intervals Female Middle Age Aged Middle Aged: 45-64 years Aged: 65+ years Female ab: Simple Summary: Drugs known as cyclin-dependent kinase 4/6 inhibitors are commonly used together with hormone therapy as the first treatment for people with hormone receptor-positive, HER2-negative advanced breast cancer. However, these drugs have not been directly compared in large clinical trials. This research reviewed published studies that used real-world patient data to compare how well the three available drugs, palbociclib, ribociclib, and abemaciclib, work in routine clinical practice. Most studies showed that patients had similar outcomes regardless of which drug was used, including similar time before the disease worsened and similar overall survival. Differences between studies, such as how long patients were followed and how results were analyzed, made some findings difficult to compare. Overall, this review suggests that all three treatments may have broadly similar effectiveness, which can help researchers and clinicians better understand treatment choices in everyday care. Background/Objective: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy are the standard first-line treatment for HR+/HER2− advanced/metastatic breast cancer (a/mBC), yet no head-to-head randomized trials have compared palbociclib, ribociclib, and abemaciclib. This systematic literature review (SLR) aimed to synthesize available real-world evidence (RWE) on the comparative effectiveness of these three CDK4/6i in the first-line setting. Methods: An SLR was conducted following PRISMA guidelines. Searches of MEDLINE, Embase, Cochrane, and gray literature (January 2015–September 2025) identified RWE studies reporting real-world progression-free survival (rwPFS) and/or overall survival (OS) for first-line CDK4/6i regimens. Eligible studies included adults with HR+/HER2− a/mBC receiving palbociclib, ribociclib, or abemaciclib, combined with endocrine-based therapy. Comparative outcomes were summarized qualitatively; study quality was assessed using the Newcastle–Ottawa Scale, ISPOR-AMCP-NPC questionnaire, and ESMO-GROW checklist. Results: From 13,345 records, 39 publications (32 unique studies) were identified, of which 21 were full-text studies meeting inclusion criteria. Most included studies used retrospective cohort designs, and approximately 50% evaluated all three CDK4/6is. Given the comparative nature of the included studies, quality issues were found to be related to study design and analytical approaches. Several analyses were unadjusted, and reporting of follow-up duration varied across studies, with some analyses providing incomplete follow-up information. Study sample sizes differed substantially across agents, with smaller populations generally reported for ribociclib and abemaciclib. Among the studies reporting rwPFS hazard ratios (HRs), 8/11 studies showed comparable rwPFS and 5/6 studies reported comparable OS outcomes between CDK4/6i regimens. Three full-text studies reported HRs favoring ribociclib or abemaciclib relative to palbociclib; these analyses primarily included populations receiving palbociclib, with smaller comparator cohorts for ribociclib and abemaciclib, as well as varied follow-up times. Conclusions: Most real-world studies included in the SLR suggested similar effectiveness of the three CDK4/6is in first-line HR+/HER2− a/mBC. Heterogeneity in patient characteristics, definitions of outcomes, follow-up time, sample size, and statistical approach may have important implications on study interpretability. pubtype: Academic Journal doctype: research systematic review tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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