OncoAlert 4Sight Abstracts to be Presented at #ESMO26
★★★Same topic FOURLIGHT-1 · 26 peopleatirmociclibHER2#BREASTCANCER2531 views19 likes12 reposts0 replies
ESMO Congress 2026
October 23–27, 2026 · Madrid · 5018 items
FOURLIGHT-1
★★★26 people · 27 posts
Deep dive
The treatment landscape of HR+/HER2− advanced breast cancer has been established by CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) [9], but acquired resistance remains a major challenge [9]; after adjuvant CDK4/6i, nearly 10% of patients recur during or shortly after treatment, and the efficacy of post-relapse therapy is largely unknown [10]. Current post-progression strategies are mainly biomarker-driven: next-generation oral SERDs for ESR1-mutated disease, alpelisib or capivasertib plus fulvestrant for PIK3CA-AKT-PTEN pathway alterations, and early transition to ADCs such as T-DXd for rapid progression or visceral disease [12]. Atirmociclib is described in the literature as a potential first-in-class inhibitor with significantly greater selectivity for CDK4 over CDK6; its phase 1/2a combination with endocrine therapy was well tolerated and showed antitumor activity [7].
FOURLIGHT-1, presented at ESMO 2026 in Proffered Paper 2 (abstract 1842O), is an open-label randomized phase 2 study [1][7]: patients with HR+/HER2− advanced/metastatic breast cancer progressing after adjuvant or first-line CDK4/6i were randomized 1:1 to atirmociclib (300 mg orally, twice daily, continuously) plus fulvestrant or investigator's choice (fulvestrant alone or everolimus plus exemestane), with investigator-assessed PFS as the primary endpoint; 263 patients were enrolled (126 vs 137; median age 57 years; data cutoff 12 January 2026) [7]. Numbers reported at the meeting: median PFS 9.4 vs 6.6 months, HR 0.60 (0.440–0.825), p=0.0007; ORR 19.3% vs 11.3%; CBR 61.9% vs 46.0%; neutropenia was the most common TRAE, discontinuation due to TRAEs was only 4.0%, though grade ≥3 AEs were more frequent. Live posts also noted simultaneous publication in Ann Oncol [7] and an ongoing phase 3 trial of atirmociclib in the first-line setting.
The main-site Chinese industry news independently covered the same direction: three 2026 ESMO abstracts focus on subsequent therapy for HR+/HER2− advanced breast cancer after CDK4/6i progression, involving atirmociclib, abemaciclib, and giredestrant combination regimens, respectively. This is consistent with the live information, placing FOURLIGHT-1 within the same competitive lane, but it added no new figures.
Relative to existing knowledge, the step forward from FOURLIGHT-1 is that after CDK4/6i progression, selectively inhibiting CDK4 alone plus fulvestrant still delivered a roughly 3-month PFS difference and a statistically significant HR, suggesting CDK4 remains a suppressible target in this resistance context, and the 4.0% discontinuation rate hints at potentially better tolerability—directly answering the question posed at the meeting of whether selective CDK4 inhibition can overcome CDK4/6i resistance. The limitations are equally clear: this is an open-label phase 2 with investigator-assessed PFS as the primary endpoint [7], and several live commentators emphasized the need for phase 3 validation; OS, DOR and other secondary endpoint results, as well as the breakdown between the two regimens within the investigator's-choice arm, were not disclosed in the available materials.
References
- 1.1842O 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 (FOU… · ESMO 2026 2026
- 2.LBA14 A double-blind placebo controlled randomized phase III trial of fulvestrant and ipatasertib as treatment for HER-2 negative and estrogen receptor positive (ER+) metastatic breast cancer (MBC): Overall survival results of… · ESMO 2026 2026
- 3.LBA15 Anbenitamab plus albumin-bound docetaxel in patients (pts) with HER2-positive advanced breast cancer (BC): A randomized phase III study · ESMO 2026 2026
- 4.LBA26 Short-term preoperative durvalumab for stage I TNBC: First results from the phase II UNLOCK 14 - POP-DURVA trial · ESMO 2026 2026
- 5.LBA51 Results from KEYNOTE-B49: A phase 3, randomized, double-blind study of pembrolizumab (pembro) vs placebo (pbo) plus chemotherapy (CT) in participants (pts) with HR+/HER2− advanced breast cancer (ABC) · ESMO 2026 2026
- 6.LBA96 First-line (1L) datopotamab deruxtecan (Dato-DXd) vs chemotherapy in patients (pts) with locally recurrent inoperable or metastatic triple-negative breast cancer (mTNBC) for whom immunotherapy was not an option: Explorat… · ESMO 2026 2026
- 7.Atirmociclib and fulvestrant for patients with HR+/HER2- advanced/metastatic breast cancer who progressed on a prior cyclin-dependent kinase 4/6 inhibitor: primary analysis of the randomized FourLight-1 trial · Ann Oncol 2026
- 8.Breast Cancer: Molecular Pathogenesis, Targeted Therapy, Screening, and Prevention · MedComm (2020) 2026
- 9.Alternate actions of CDK4/6 inhibitors beyond cell cycle blockade: unexplored roles in therapy resistance · Cancer Metastasis Rev 2025
- 10.Managing relapses during or after adjuvant CDK4/6 inhibitors in HR-positive/HER2-negative early breast cancer: an emerging challenge · ESMO Open 2025
- 11.WITHDRAWN: From CDK4/6 to CDK2 and KAT: Evolving therapeutic approaches in HR+/HER2- breast cancer · Breast 2026
- 12.Beyond CDK4/6 Inhibition: Current Strategies in Hormone Receptor-Positive Metastatic Breast Cancer · Curr Treat Options Oncol 2026
Floor
OncoAlert@OncoAlert Aya Mohamed | MSc, MD 🎗@Dr_Oncologista ★★★Same topic FOURLIGHT-1 · 26 peopleatirmociclibHER2#BREASTCANCER276 views14 likes8 reposts0 repliesElisa Agostinetto@ElisaAgostinett At #ESMO26 Proffered Paper 2️⃣ on #breastcancer
Elisabetta Bonzano MD, PhD@to_be_elizabeth 📌 Proffered paper 2: Breast cancer, early and advanced stage
Prof. Dr. Ahmet Dirican@dr_dirican Can selective CDK4 inhibition overcome resistance to CDK4/6 inhibitors?
Same topic FOURLIGHT-1 · 26 peopleFOURLIGHT-3atirmociclib#BREASTCANCER#PRECISIONONCOLOGY#CDK482 views4 likes4 reposts0 repliesCarmen Criscitiello@CarmenCriscit Guilherme Nader Marta@GuiNaderMarta FourLight-1 presented by @antgiorda at #ESMO26
Dra. María Natalia Gandur Quiroga@nataliagandur 🧬 After progression on a CDK4/6 inhibitor, is it time to rethink whether the class can still work?
引用@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
Same topic FOURLIGHT-1 · 26 peopleatirmociclibHER2#BREASTCANCER#CDK46#ENDOCRINETHERAPY#PRECISIONONCOLOGY113 views3 likes1 repost0 repliesMirrors of Medicine@mirrorsmed Looking forward to this one at #ESMO26 👀
引用@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
Kazuki Nozawa, MD@kazuki_nozawa Kristina Jankovic, MD@JankovicK Same topic FOURLIGHT-1 · 26 peopleatirmociclib#ATIRMOCICLIB#BREASTCANCER30 views1 like1 repost0 repliesPhilippe Aftimos, MD @aftimosp Mali Barbi, MD MSc | Breast & Gyn Oncologist@DrBarbiOnc After CDK4/6i in HR+ MBC, the control arm is the story at #ESMO2026.
引用@#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
MeDucation@MeDucationai 引用@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
ESMO - Eur. Oncology@myESMO Same topic FOURLIGHT-1 · 26 peopleatirmociclib#ADVANCEDBREASTCANCER#CLINICALTRIAL#INSIGHTSBYESMO#BREASTCANCER138 views0 likes0 reposts0 repliesProf Andrew Wardley 🦋@AndrewWardley Breastcancer.org@Breastcancerorg Same topic FOURLIGHT-1 · 26 peopleatirmociclibHER2#BREASTCANCER#BREASTCANCERRESEARCH#INSIGHTSBYESMO#METAVIVOR34 views0 likes0 reposts0 repliesOncologyEducation@OncEd Nurullah İlhan,MD@drnurullahilhan FOURLIGHT-1: HR+/HER2− breast cancer after CDK4/6i.
ScienceLink@sciencelinkonco #ScienceLink #Madrid2026 #ESMO26 #FOURLIGHT1 #atirmociclib
Same topic FOURLIGHT-1 · 26 peopleatirmociclibHER2#SCIENCELINK#MADRID2026#FOURLIGHT1#ATIRMOCICLIB11 views0 likes0 reposts0 repliesMirrors of Medicine@mirrorsmed Giampaolo Bianchini@BianchiniGP 🔥 FOURLIGHT-1 demonstrates atirmociclib efficacy post-CDK4/6i
Pablo Jara Martin@pablojaramartin Yakup Ergün@dr_yakupergun Dana-Farber News@DanaFarberNews Annals of Oncology@Annals_Oncology