🧬 After progression on a CDK4/6 inhibitor, is it time to rethink whether the class can still work?
@OncoAlert
At #ESMO26, randomized phase II FOURLIGHT-1 evaluated atirmociclib + fulvestrant versus investigator’s choice in HR+/HER2– advanced #BreastCancer after prior CDK4/6 inhibition.
📊 n=263
➡️ Median PFS: 9.4 vs 6.6 months
HR 0.60 (0.440–0.825)
➡️ ORR: 19.3% vs 11.3%
➡️ CBR: 61.9% vs 46.0%
⚠️ Neutropenia was the most common TRAE, but treatment discontinuation due to TRAEs was only 4.0%
🎯 Why this matters: resistance to one CDK4/6 inhibitor may not mean the pathway is exhausted.
For me, the key signal here is that a next-generation CDKi can recapture meaningful disease control after prior CDK4/6 exposure.
The next questions are the ones that will define the field:
🔹 who remains CDK-dependent?
🔹 which resistance mechanisms matter most?
🔹 and can biomarkers help us identify who should receive another CDK strategy versus switching pathway entirely?
Excellent work from @antgiorda and the FOURLIGHT-1 investigators.
Pinging @matteolambe @aftimosp @E_de_Azambuja @DrSGraff @ErikaHamilton9 @hoperugo @stolaney1 @BianchiniGP @kevinpunie @GaiaGriguolo
#OncoAlert #ESMO26 #BreastCancer #CDK46 #EndocrineTherapy #PrecisionOncology
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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 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在 X 查看被引用的帖子
Source: Dra. María Natalia Gandur Quiroga · x.com