October 23–27, 2026 · Madrid · 3132 items
23 people · 24 posts · 2 abstracts
Heat now 9·Peak in the comparable set 14 (Oct 24 18:00)·Change over 24h in the comparable set –·Participants now 19
In the targeted-therapy landscape of HR+/HER2– breast cancer, CDK4/6 inhibitors combined with endocrine therapy are already a core component, and PI3K/AKT/mTOR inhibitors (the everolimus + exemestane used in this study's control arm belongs to this class) are likewise an established category, yet resistance and toxicity remain the main bottlenecks limiting efficacy, and how to select and sequence subsequent therapy after resistance is still an unresolved clinical question [6].
At ESMO26, FOURLIGHT-1 was presented: a randomized phase 2 trial (n=263) enrolling patients with HR+/HER2– advanced/metastatic breast cancer that progressed on prior CDK4/6 inhibitor, randomized to atirmociclib + fulvestrant versus investigator's choice (fulvestrant, or everolimus + exemestane), with investigator-assessed PFS as the primary endpoint. Median PFS was 9.4 vs 6.6 months, HR 0.60 (0.440–0.825), 1-sided p=0.0007; ORR in patients with measurable disease was 19.3% vs 11.3%, and CBR was 61.9% vs 46.0%. On safety, the most common TRAE was neutropenia (46.4%), and discontinuation of atirmociclib due to TRAEs was only 4.0%. The presenter was Antonio Giordano, and the on-site conclusion positioned it as the first next-generation CDKi to show significant and clinically meaningful PFS improvement after prior CDK4/6i, with a manageable safety profile.
The notable step forward is that atirmociclib is a CDK4-selective inhibitor designed to spare CDK6 in order to ease the neutropenia that limits current CDK4/6 inhibitors; this readout suggests that resistance to one CDK4/6 inhibitor does not necessarily mean the pathway is exhausted, and a next-generation CDK inhibition strategy can still recapture meaningful disease control after prior exposure. The on-site discussion also flagged the questions that will define the field: who remains CDK-dependent, which resistance mechanisms matter most, and whether biomarkers can help identify who should receive another CDK strategy versus switching pathway entirely.
As for limitations, FOURLIGHT-1 is phase 2 in scale (n=263), the primary endpoint was investigator-assessed PFS, and overall survival data, biomarker stratification analyses, and any subsequent phase 3 plans were not disclosed; whether this can change clinical practice after prior CDK4/6 inhibitor therapy remains to be confirmed.
Efficacy and safety of atirmociclib (ATI) + fulvestrant (FUL) in patients (pts) with HR+/HER2– advanced/metastatic breast cancer (mBC) who progressed on prior CDK4/6 inhibitor (CDK4/6i) in a randomized phase 2 study (FOURLIGHT-1)
https://esmocongress.esmo.orgFOURLIGHT-1
https://esmocongress.esmo.orgOncoAlert 4Sight Abstracts to be Presented at #ESMO26
At #ESMO26 Proffered Paper 2️⃣ on #breastcancer
📌 Proffered paper 2: Breast cancer, early and advanced stage
Can selective CDK4 inhibition overcome resistance to CDK4/6 inhibitors?
FourLight-1 presented by @antgiorda at #ESMO26
🧬 After progression on a CDK4/6 inhibitor, is it time to rethink whether the class can still work?
OncoAlert 4Sight Abstracts to be Presented at #ESMO26 Efficacy and Safety of Atirmociclib + Fulvestrant in Patients With HR+/HER2– Advanced/Metastatic Breast Cancer Who Progressed on Prior CDK4/6 Inhibitor in a Randomized Phase 2 Study (FOURLIGHT-1) @antgiorda 🔬 Randomized phase 2 (n=263): atirmociclib + fulvestrant vs investigator’s choice (fulvestrant or everolimus + exemestane) in HR+/HER2– mBC after prior CDK4/6i. Primary: investigator-assessed PFS. ➡️ Median PFS 9.4 vs 6.6 mo; HR 0.60 (0.440–0.825); 1-sided p=0.0007 ➡️ ORR in patients with measurable disease: 19.3% vs 11.3%; CBR: 61.9% vs 46.0% ➡️ Atirmociclib discontinuation due to TRAEs: 4.0%; most common TRAE neutropenia (46.4%) ✅ First next-generation CDKi to show significant and clinically meaningful PFS improvement after prior CDK4/6i, with a manageable safety profile. #BreastCancer 🎙️ Antonio Giordano (4Sight Made from Abstracts publicly available at the ESMO website) @matteolambe @aftimosp @E_de_Azambuja @DrSGraff @ErikaHamilton9 @hoperugo @stolaney1 @BianchiniGP @aftimosp @kevinpunie @ElisaAgostinett @to_be_elizabeth @GaiaGriguolo @JankovicK @raalbany @JavierCortesMD @JaniceTNBCmets @Prof_Nadia_H @LoiSher @jamecancerdoc @Lucarecco @Dr_Oncologista @guiandri76
Looking forward to this one at #ESMO26 👀
OncoAlert 4Sight Abstracts to be Presented at #ESMO26 Efficacy and Safety of Atirmociclib + Fulvestrant in Patients With HR+/HER2– Advanced/Metastatic Breast Cancer Who Progressed on Prior CDK4/6 Inhibitor in a Randomized Phase 2 Study (FOURLIGHT-1) @antgiorda 🔬 Randomized phase 2 (n=263): atirmociclib + fulvestrant vs investigator’s choice (fulvestrant or everolimus + exemestane) in HR+/HER2– mBC after prior CDK4/6i. Primary: investigator-assessed PFS. ➡️ Median PFS 9.4 vs 6.6 mo; HR 0.60 (0.440–0.825); 1-sided p=0.0007 ➡️ ORR in patients with measurable disease: 19.3% vs 11.3%; CBR: 61.9% vs 46.0% ➡️ Atirmociclib discontinuation due to TRAEs: 4.0%; most common TRAE neutropenia (46.4%) ✅ First next-generation CDKi to show significant and clinically meaningful PFS improvement after prior CDK4/6i, with a manageable safety profile. #BreastCancer 🎙️ Antonio Giordano (4Sight Made from Abstracts publicly available at the ESMO website) @matteolambe @aftimosp @E_de_Azambuja @DrSGraff @ErikaHamilton9 @hoperugo @stolaney1 @BianchiniGP @aftimosp @kevinpunie @ElisaAgostinett @to_be_elizabeth @GaiaGriguolo @JankovicK @raalbany @JavierCortesMD @JaniceTNBCmets @Prof_Nadia_H @LoiSher @jamecancerdoc @Lucarecco @Dr_Oncologista @guiandri76
After CDK4/6i in HR+ MBC, the control arm is the story at #ESMO2026.
#FINER fulvestrant +/- ipatasertib (AKTi) 45% of pts were pathway altered PFS lengthened in ITT HR 0.68 and AKT altered cohorts HR 0.55 93% diarrhea, pretty high G2/3 rates #ESMO26 #ESMOAmbassadors
FOURLIGHT-1 | ESMO 2026 Can CDK4 inhibition work after CDK4/6 progression? 1. Population: 263 patients with HR+/HER2− advanced breast cancer after prior CDK4/6 inhibitor. 2. Arms: Atirmociclib + fulvestrant vs investigator’s choice (fulvestrant or everolimus + exemestane). 3. Median PFS: 9.4 vs 6.6 months (HR 0.60). 4. ORR: 19.3% vs 11.3%. 5. Clinical benefit ≥24 weeks: 61.9% vs 46.0%. 6. Safety: Neutropenia 46.4%; leukopenia 32.8%; treatment-related discontinuation 4%. 7. Take-home: Promising phase II PFS benefit. OS immature; phase III confirmation needed. Ref: Giordano A, et al. FOURLIGHT-1. ESMO 2026; Abstract 1842O. #ESMO26 #BreastCancer #MVOnco
FOURLIGHT-1: HR+/HER2− breast cancer after CDK4/6i.
#ScienceLink #Madrid2026 #ESMO26 #FOURLIGHT1 #atirmociclib
🔥 FOURLIGHT-1 demonstrates atirmociclib efficacy post-CDK4/6i