# CDK4/6 inhibitors

Source: https://onco.cc/technologies/cdk46-inhibitor/  
OnCo record `cdk46-inhibitor` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Pills that stop the cell-division engine, added to hormone therapy for the most common type of breast cancer.

## Summary

Palbociclib, ribociclib, abemaciclib with endocrine therapy: PFS roughly doubled and, for ribociclib and abemaciclib, overall survival improved in advanced HR+/HER2- disease. Ribociclib (NATALEE) and abemaciclib (monarchE) are approved as adjuvant therapy for high-risk early disease. 2026: palbociclib approved as maintenance in HR+/HER2+ disease (PATINA).

## Fields

- Kind: Technology
- Status: approved
- Last checked: 2026-09-04
- Principle: Block RB phosphorylation, arresting cells in G1.
- Since: 2015
- Strengths: Oral, well tolerated; Adjuvant survival benefit
- Limitations: Neutropenia, diarrhoea (abemaciclib), QT (ribociclib); Resistance via RB loss, CDK2, cyclin E

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/CDK_inhibitor
- Wikipedia: https://en.wikipedia.org/wiki/CDK_inhibitor

## Connected records

- pairings: [CDK4/6 inhibitor + endocrine therapy](https://onco.cc/pairings/cdk46-plus-endocrine/), [Oral SERD + CDK4/6 inhibitor after ESR1 emergence](https://onco.cc/pairings/oral-serd-plus-cdk46-after-esr1/)
- cancers: [HER2-positive breast cancer](https://onco.cc/cancers/breast-her2-positive/), [High-risk early HR-positive breast cancer](https://onco.cc/cancers/hr-positive-early-high-risk/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Invasive lobular carcinoma of the breast](https://onco.cc/cancers/invasive-lobular-carcinoma/), [Male breast cancer](https://onco.cc/cancers/male-breast-cancer/)
- fronts: [Hormonal Therapy](https://onco.cc/fronts/hormonal/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- targets: [CDK4/6](https://onco.cc/targets/cdk4-6/), [Estrogen receptor (ERα)](https://onco.cc/targets/estrogen-receptor/)
- drugs: [Abemaciclib](https://onco.cc/drugs/abemaciclib/), [Atirmociclib](https://onco.cc/drugs/atirmociclib/), [Dalpiciclib](https://onco.cc/drugs/dalpiciclib/), [Palbociclib](https://onco.cc/drugs/palbociclib/), [Ribociclib](https://onco.cc/drugs/ribociclib/)
- key papers: [monarchE: two years of abemaciclib after surgery in high-risk, hormone-receptor-positive early breast cancer](https://onco.cc/key-papers/paper-monarche-jco-2020/), [NATALEE: three years of ribociclib after surgery in a broad population of hormone-receptor-positive early breast cancer](https://onco.cc/key-papers/paper-natalee-nejm-2024/), [Sherr and Roberts 1999: CDK inhibitors as regulators of the G1 phase](https://onco.cc/key-papers/paper-sherr-roberts-cdk-inhibitors-genesdev-1999/)
- trials: [A Comparative Study of AZD9833 Plus Palbociclib Versus Anastrozole Plus Palbociclib in Patients With ER-Positive HER2 Negative Breast Cancer Who Have Not Received Any Systemic Treatment for Advanced Disease](https://onco.cc/trials/nct04711252/), [A Phase II Study Evaluating the Efficacy and Safety of Inavolisib Plus Ribociclib Plus Fulvestrant Versus Placebo Plus Ribociclib Plus Fulvestrant in Participants With Advanced Breast Cancer](https://onco.cc/trials/nct07405801/), [A Phase IIIb Study to Evaluate Camizestrant Plus Ribociclib in ER-positive, HER2-negative Advanced Breast Cancer](https://onco.cc/trials/nct07647328/), [A Study Comparing Abemaciclib Plus Temozolomide to Temozolomide Monotherapy in Children and Young Adults With High-grade Glioma Following Radiotherapy](https://onco.cc/trials/nct06413706/), [A Study of Abemaciclib (LY2835219) Combined With Fulvestrant in Women With Hormone Receptor Positive HER2 Negative Breast Cancer](https://onco.cc/trials/nct02107703/), [A Study of Abemaciclib (LY2835219) in Participants With Breast Cancer](https://onco.cc/trials/nct02763566/), [A Study of Abemaciclib (LY2835219) in Participants With Previously Treated KRAS Mutated Lung Cancer](https://onco.cc/trials/nct02152631/), [A Study of Abemaciclib (LY2835219) Plus Tamoxifen or Abemaciclib Alone in Women With Metastatic Breast Cancer](https://onco.cc/trials/nct02747004/), [A Study of Abemaciclib (LY2835219) With Abiraterone in Men With Prostate Cancer That Has Spread to Other Parts of the Body and is Expected to Respond to Hormonal Treatment (Metastatic Hormone-Sensitive Prostate Cancer)](https://onco.cc/trials/nct05288166/), [A Study of Abiraterone Acetate Plus Prednisone With or Without Abemaciclib (LY2835219) in Participants With Prostate Cancer](https://onco.cc/trials/nct03706365/), [A Study of Belzutifan (MK-6482) in Combination With Palbociclib Versus Belzutifan Monotherapy in Participants With Advanced Renal Cell Carcinoma (MK-6](https://onco.cc/trials/nct05468697/), [A Study to Evaluate the Effect of GDC-4198 Alone and in Combination With Giredestrant Versus Abemaciclib and Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor-Negative (HER2-) Breast Cancer](https://onco.cc/trials/nct07100106/), [A Study to Learn About the Study Medicine (Called PF-07220060 in Combination With PF-07104091) In Participants With Breast Cancer and Solid Tumors](https://onco.cc/trials/nct05262400/), [A Study to Learn About Vepdegestrant When Given With PF-07220060 to People With Advanced or Metastatic Breast Cancer.](https://onco.cc/trials/nct06206837/), [CAMPFIRE: A Study of Abemaciclib (LY2835219) in Participants With Ewing's Sarcoma](https://onco.cc/trials/nct05440786/), [Clinical Study of HRS-8080 in Combination With Dalpiciclib Isethionate Tablets in Patients With Unresectable or Metastatic Breast Cancer](https://onco.cc/trials/nct06167694/), [DAWNA-1](https://onco.cc/trials/dawna-1/), [Evaluation of Lasofoxifene Combined With Abemaciclib Compared With Fulvestrant Combined With Abemaciclib in Locally Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation](https://onco.cc/trials/nct05696626/), [FOURLIGHT-1](https://onco.cc/trials/fourlight-1/), [Gedatolisib Plus Fulvestrant With or Without Palbociclib vs Standard-of-Care for the Treatment of Patients With Advanced or Metastatic HR+/HER2- Breast Cancer (VIKTORIA-1)](https://onco.cc/trials/nct05501886/), [Lung-MAP (SWOG S1400 and S1900)](https://onco.cc/trials/lung-map/), [MONALEESA-2](https://onco.cc/trials/monaleesa-2/), [MONARCH 3](https://onco.cc/trials/monarch-3/), [monarchE](https://onco.cc/trials/monarche/), [NATALEE](https://onco.cc/trials/natalee/), [National Lung Matrix Trial](https://onco.cc/trials/national-lung-matrix-trial/), [Palazestrant in Combination With Ribociclib for the First-line Treatment of ER+/HER2- Advanced Breast Cancer](https://onco.cc/trials/nct07085767/), [PALLAS & PENELOPE-B](https://onco.cc/trials/pallas-penelope-b/), [PALOMA-2](https://onco.cc/trials/paloma-2/), [PATINA](https://onco.cc/trials/patina/), [PENELOPE-B](https://onco.cc/trials/penelope-b/), [Phase 3 Study of Gedatolisib as First-Line Treatment for Patients With HR-Positive, HER2-Negative Advanced Breast Cancer (VIKTORIA-2)](https://onco.cc/trials/nct06757634/), [Phase III Study ：SHR6390/Placebo Combined With Endocrine Therapy for the Adjuvant Treatment of Hormone Receptor Positive,Human Epidermal Receptor 2 Ne](https://onco.cc/trials/nct04842617/), [Phase IIIb Study of Ribociclib + ET in Early Breast Cancer](https://onco.cc/trials/nct05827081/), [postMONARCH](https://onco.cc/trials/postmonarch/), [Probiotics for Abemaciclib-Induced Abdominal Discomfort.](https://onco.cc/trials/nct07605728/), [Safety and Tolerability of TNG456 Alone and in Combination With Abemaciclib in Patients With Solid Tumors With MTAP Loss](https://onco.cc/trials/nct06810544/), [Study for Participants Continuing From Pfizer-sponsored Palbociclib (a Study Medicine) Studies](https://onco.cc/trials/nct05226871/), [Study of Abemaciclib and Elacestrant in Participants With Brain Metastasis Due to ER+/HER-2- Breast Cancer](https://onco.cc/trials/nct05386108/), [Study of ECI830 Single Agent or in Combination in Patients With Advanced HR+/HER2- Breast Cancer and in Patients With Other Advanced Solid Tumors](https://onco.cc/trials/nct06726148/), [Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors](https://onco.cc/trials/nct03709680/), [Study of PF-07220060 With Letrozole in Adults With HR-positive HER2-negative Breast Cancer Who Have Not Received Anticancer Treatment for Advanced/Metastatic Disease](https://onco.cc/trials/nct06760637/), [Study to Evaluate the Safety and Tolerability of Camizestrant in Combination With Atirmociclib in Women With Advanced Breast Cancer](https://onco.cc/trials/nct07427394/), [Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors](https://onco.cc/trials/nct04557449/), [TACTIVE-U: A Study to Learn About the Study Medicine (Vepdegestrant) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer (Sub-Study A)](https://onco.cc/trials/nct05548127/), [TACTIVE-U: A Study to Learn About the Study Medicine (Vepdegestrant) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer (Sub-Study B)](https://onco.cc/trials/nct05573555/), [TAPUR (Targeted Agent and Profiling Utilization Registry)](https://onco.cc/trials/tapur/), [Vepdegestrant (ARV-471/PF-07850327) + Palbociclib vs Letrozole + Palbociclib in ER(+)/HER2(-) Advanced Breast Cancer](https://onco.cc/trials/nct05909397/)
- technologies: [Endocrine therapy (SERMs, AIs, SERDs)](https://onco.cc/technologies/endocrine-therapy/)
- pathways: [Cellular senescence](https://onco.cc/pathways/senescence/), [Oestrogen receptor signalling](https://onco.cc/pathways/er-signaling/), [The cell-cycle engine (cyclins & CDKs)](https://onco.cc/pathways/cell-cycle-engine-cdks/), [Tumour dormancy](https://onco.cc/pathways/tumor-dormancy/)
- people: [Gabriel N. Hortobagyi](https://onco.cc/people/gabriel-hortobagyi/), [Massimo Cristofanilli](https://onco.cc/people/massimo-cristofanilli/), [Richard S. Finn](https://onco.cc/people/richard-finn/), [Stephen Johnston](https://onco.cc/people/stephen-johnston/)
- bottlenecks: [Wrong doses](https://onco.cc/bottlenecks/b-dose-optimisation/)
- ideas: [Combination baskets defined by resistance mechanism rather than by cancer type](https://onco.cc/ideas/idea-tr2-resistance-mechanism-baskets/), [Eradicate dormant cancer cells: a programme to wake and kill or lock asleep disseminated cells](https://onco.cc/ideas/idea-moon-dormancy-eradication-programme/), [Pharmacist interaction check before every oral cancer-drug prescription](https://onco.cc/ideas/idea-acc-pharmacist-interaction-review-oral-anticancer/), [Start low and step up: individualised titration of oral cancer drugs, randomised](https://onco.cc/ideas/idea-tr1-start-low-titrate-up-oral-agents/), [Time immunotherapy to the moment targeted drugs make tumours visible](https://onco.cc/ideas/idea-bio1-immunopeptidome-timing/)
- terms: [Aromatase inhibitor](https://onco.cc/terms/aromatase-inhibitor/), [Cell cycle](https://onco.cc/terms/cell-cycle/), [Checkpoint (two meanings)](https://onco.cc/terms/checkpoint/), [Hallmark: evading growth suppressors](https://onco.cc/terms/evading-growth-suppressors/), [Hallmarks of cancer as a synthesis of the theories](https://onco.cc/terms/hallmarks-synthesis/), [Hormone therapy](https://onco.cc/terms/hormone-therapy/), [Inhibitor](https://onco.cc/terms/inhibitor/), [Kinase](https://onco.cc/terms/kinase/), [Targeted therapy](https://onco.cc/terms/targeted-therapy-term/)
- institutions: [Breast Cancer Research Foundation](https://onco.cc/institutions/bcrf/), [Comprehensive Cancer Center Vienna, Medical University of Vienna / AKH](https://onco.cc/institutions/ccc-vienna/), [Edinburgh Cancer Centre / CRUK Scotland Centre](https://onco.cc/institutions/edinburgh-cancer-centre/), [Istituto Oncologico Veneto IRCCS](https://onco.cc/institutions/iov-veneto/), [UNC Lineberger Comprehensive Cancer Center](https://onco.cc/institutions/unc-lineberger/)
- roadmaps: [Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test](https://onco.cc/roadmaps/hormonal-therapy-roadmap/)
- companies: [Austrian Breast & Colorectal Cancer Study Group](https://onco.cc/companies/abcsg/), [G1 Therapeutics](https://onco.cc/companies/g1-therapeutics/), [GEICAM Spanish Breast Cancer Group](https://onco.cc/companies/geicam/), [SOLTI Cancer Research Group](https://onco.cc/companies/solti/)

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