Living dossier · Competitive landscape

CDK4/6 in HR-positive breast cancer

Primary identifiers: 8
Sponsors tracked: 7
Evidence types: 2 of 3
Last refreshed: 2026-07-28 · monthly

MightyRayn panel synthesis

OmniRayn’s reading of this landscape — our interpretation, not a registry fact

The live question here is no longer which inhibitor but what to do when one stops working, and the registry has quietly reorganised around that. Most active Phase 3 work sits in the adjuvant and early-disease setting rather than metastatic first line — the class is being pushed earlier rather than deeper. Meanwhile the most consequential recent trial tested no new inhibitor at all: it monitored circulating tumour DNA for an emergent resistance mutation and swapped the endocrine partner while keeping the CDK4/6 inhibitor in place. That reframes the class as a backbone to be preserved rather than a drug to be replaced, and it pulls ctDNA surveillance into the competitive picture. The corollary for anyone entering: the comparator is a combination and a monitoring strategy, not a molecule.

Programs and primary evidence

Sponsor	Asset	Phase	Mechanism	Primary source
Novartis Pharmaceuticals	Ribociclib (NATALEE)	3	CDK4/6 inhibitor with endocrine therapy, adjuvant	NCT03701334 — Adjuvant ribociclib plus endocrine therapy in HR-positive, HER2-negative early breast cancer
Novartis Pharmaceuticals	Ribociclib (Adjuvant WIDER)	3	CDK4/6 inhibitor in a close-to-clinical-practice population	NCT05827081 — Phase 3b characterising adjuvant ribociclib plus endocrine therapy outside trial-idealised populations
West German Study Group	Ribociclib (ADAPTcycle)	3	CDK4/6 inhibitor plus endocrine therapy versus chemotherapy	NCT04055493 — Marker-adjusted personalised therapy comparing endocrine therapy plus ribociclib against chemotherapy in intermediate-risk early disease
Japanese Foundation for Cancer Research	Abemaciclib (JCOG2313 AURA)	3	CDK4/6 inhibitor in locoregional recurrence	NCT07190443 — Adjuvant abemaciclib in patients with locoregional recurrence of HR-positive, HER2-negative disease
Celcuity	Gedatolisib + palbociclib (VIKTORIA-2)	3	PI3K/mTOR inhibitor added to a CDK4/6 backbone versus a different CDK4/6 inhibitor	NCT06757634 — First-line comparison of gedatolisib with palbociclib and endocrine therapy against ribociclib and endocrine therapy
First Affiliated Hospital, Nanjing Medical University	Dalpiciclib (adjuvant)	2	CDK4/6 inhibitor with endocrine therapy, adjuvant	NCT06341894 — Adjuvant dalpiciclib with endocrine therapy in HR-positive, HER2-negative early breast cancer
Institut Curie	SERENA-6 randomised trial report	—	ctDNA-guided switch of the endocrine partner while the CDK4/6 inhibitor continues	10.1056/NEJMoa2502929 — Trial reported longer investigator-assessed progression-free survival when patients with an emergent ESR1 mutation switched endocrine partner and continued the CDK4/6 inhibitor, versus continuing the aromatase inhibitor
University of Palermo	review	—	CDK4/6-Rb-E2F axis; sensitivity and resistance determinants	10.1016/j.drup.2024.101103 — Mechanisms of sensitivity and resistance to CDK4/6 inhibition, including effects on the breast stromal compartment; notes there is no established standard next-line treatment for acquired resistance

Method and limits

Programs are enumerated from primary registries (ClinicalTrials.gov, PubMed). A program appears here only if a primary record links this target to this indication as a therapeutic hypothesis — associations and risk markers are excluded by design.
Every claim above carries the identifier it rests on. We report what the record states; we do not assert efficacy, and computational findings are pending wet-lab confirmation.
Absence is not evidence of absence: unregistered, non-US and stealth-stage programs are not visible to these sources.
This page refreshes monthly (no net-new primary entity in 369 days). Mechanism classifications are our reading of the public record and may be revised.

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