Phase III giredestrant (oral SERD) + everolimus vs. physician's choice ET + everolimus in ER+/HER2- advanced breast cancer post-CDK4/6i. Roche · ESMO 2025 / SABCS 2025 / ESMO Breast 2026.
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Trial slides shared by KOLs at ESMO 2025 / SABCS 2025. Click any image to expand. OCR text extracted via AWS Textract.
[Slide 1] SABCS 2025 METASTATIC HR+ HIGHLIGHTS Study Patient Population Treatment / Comparator Key Findings HR+/HER2+ with high - PFS 7mos vs. 13.9mos (HR 0.67) Chemo + maint ET AMBRE tumor burden - ORR 29.2% VS. 35.2% vs. (involving visceral - DoR 7.4mos vs. 10.9mos (HR 0.46, ET + Abemaciclib sites) p=0.023) - PFS with ILC 20.5mos vs. 9.4mos (HR 0.56) MONALEESA-3 - PFS with ILC 1L pts 59.6mos vs. Ribociclib + Fulvestrant HR+/HER2- ABC post 40mos (HR 0.54) Update vs. ET - OS with ILC 51.2mos vs. 30.8mos (ILC Subtype) Placebo + Fulvestrant (HR 0.62) - OS with ILC 1L pts 59.6mos vs. 40mos (HR 0.54) HR+/HER2- ABC Gedatolisib + Palbo + Fulv - PFS by bone mets status triplet NR progression on/after VS. VS. NR VS. 8.2mos VIKTORIA-1 CDK4/6i + NSAI, <2 Gedatolisib + Fulv - PFS in non-bone mets 9.3mos VS. prior ET for ABC, VS. 7.3mos VS. 1.9mos PIK3CA WT Fulv alone Camizestrant + CDK4/6i - Time to first subsequent therapy HR+/HER2- ABC post 16.6mos. VS. 9.2mos SERENA-6 AI + CKD4/6i for at vs. AI + CDK4/6i - Time to second subsequent least 6mos with ESRlm therapy 25.7mos vs. 19.4mos - PFS in ESRlm 9.99mos vs. 5.45mos HR+/HER- ABC <2 Giredestrant + Everolimus - PFS in ITT 8.77mos VS. 5.49mos prior lines of ET, evERA vs. - PFS in duration of prior CDK4/6i progressive disease ET + Everolimus <12mos, 5.55mos VS. 3.8lmos during/post CDK4/6i - PFS in duration of prior CDK4/6i 212mos 9.23mos VS. 5.55mos ER+, HER2- ABC - OS in all patients, NR vs. 34.4mos recurrence on or Imlunestrant + Abemaciclib - PFS with ESRlm 11.1mos vs. 5.5mos EMBER-3 after 12 mos of vs. (HR 0.49) completion of AI+/- Imlunestrant - PFS without ESRlm 9.2mos vs. CDK4/6i 5.5mos (HR 0.64) Sacituzumab HR+/HER2-, ABC post - 12mos PFS rate by BICR 40% VS. ASCENT-07 VS. 37% (HR 0.85, p=0.130) ET Physician's choice - OS NR VS. NR (HR 0.72, p=0.029) Website: ONC x @OncBrothers www.oncbrothers.com
[Slide 1] Managing HR+/HER2- mBC Patients in 2025 ET + CDK4/6 Inavolisib + Palbociclib 1st-Line Therapy inhibitor + Fulvestrant Progression during or within 12 months of Repeat Molecular Testing at Progression completing adjuvant endocrine therapy (plasma preferred) ESR1m PIK3CA AKT Pathway gBRCAm WT 2nd-Line Therapy Fulvestrant + Fulvestrant + CDK4/6i Elacestrant Apelisib Fulvestrant + Olaparib or or Imlunestrant or Capivasertib Talazoparib ET + Capivasertib Everolimus Chemotherapy: HER2 IHC low HER2 IHC 0 Useful in Certain Circumstances: After ET Options Capecitabine TMB-H or MSI-H: Dostarlimab or Pembrolizumab Paclitaxel NTRK Fusion: Entrectinib or Other SG Larotrectinib T-DXd Dato-DXd RET Fusion: Selpercatinib 21 previous lines of chemo in metastatic Progression 21 ET, taxane, and CDK4/6i; setting or disease recurrence s6 months 22 to s4 lines of chemo or not a candidate after adjuvant therapy 21 line of ET for T-DXd Lopetegui L et al. JCO Oncol Practice. 2024;00:1-10.; NCCN Guidelines V5.2025
[Slide 1] evERA Breast Cancer INV-PFS and interim OS in patients without ESR1m detected (exploratory analysis) INV-PFS Interim OS 100. Giredestrant 100 SOC ET + everolimus everolimus n 81 n 85 Events, n (%) 63 (77.8) 74 (87.1) 80 5.72 5.52 80 Median, mo (95% CI) (5.45,7.98) (3.88, 6,51) Stratified HR (95% CI) 0.84 (0.59, 1.18) 60 60 INV-PFS (%) os (%) 40 40 Giredestrant SOC ET + + everolimus everolimus n 81 n 85 20 20 Events, n (%) 21 (25.9) 27 (31.8) NE NE Median, mo (95% CI) (NE, NE) (27.01, NE) Stratified HR 0 0 (95% CI) 0.79 (0.44, 1.40) 0 3 6 9 12 15 18 21 24 27 30 0 3 6 9 12 15 18 21 24 27 30 33 36 No. at risk Time (mo) No. at risk Time (mo) Giredestrant everolimus 81 64 34 27 19 16 8 1 1 1 Giredestrant everolimus 81 78 74 71 70 66 56 28 14 3 SOC ET everolimus 85 64 33 25 17 12 6 2 2 1 SOC ET everolimus 85 80 74 69 65 59 49 28 16 6 1 Data cutoff 16 July 2025 CI, confidence interval, HR, hazard ratio; INV-PFS, investigator-assessed progression-free survival; mo, months; NE, not evaluable; OS, overall survival; SOC ET, standard of care endocrine therapy. Presented by: Erica L. Mayer, MD, MPH. BERLIN 2025 ESMO congress Content of this presentation is copyright and responsibility of the author. Permission is required for re-use.
[Slide 1] SAN ANTONIO BREAST CANCER SYMPOSIUM® DECEMBER 9-12, 2025 HENRY B. GONZALEZ CONVENTION CENTER SAN ANTONIO, TX UT Health AAGR - - unerscan Emication Mays Lancer Jenn - - REPREST Imlunestrant With or Without Abemaciclib in Advanced Breast Cancer: Updated Efficacy Results From the Phase 3 EMBER-3 Trial Komal L. Jhaveri1, Patrick Neven², Monica Lis Casalnuovo³, Sung-Bae Kim4, Eriko Tokunaga⁵, Philippe Aftimos⁶, Cristina Saura⁷, Joyce O'Shaughnessy Nadia Harbeck Lisa A. Carey¹⁰, Giuseppe Curigliano11, Junichiro Watanabe¹², Elgene Lim13, Juan Huang14, Zhang Qingyuan15, Antonio Llombart-Cussac¹⁶, Chiun-Sheng Huang17, Bhardwaj Desai18, Yemag Limay18, Xuejing Aimee Wang18, Shanshan Cao¹⁸, François-Clement Bidard19 Memorial Sloan Kettering Cancer Center, New York, USA; University Hospitals Leuven, Leuven, Belgium; Hospital Maria Curie, Buenos Aires, Argentina; Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; Mnstitut Jules Bordet, Brussels, Belgium; Vall f Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; "Baylor University Medical Center, Texas Oncology, US Oncology, Dallas, USA; Breast Center, Department of Obstetrics and Gynecology, and LMO University Hospital, Munich, Germany: University of North Carolina at Chapel Hill, Chapel Hill, USA; "University of Milano, Milan, Italy, and European Institute of Oncology, IRCCS, Milano, Italy; Juntendo University Graduate School of Medicine, Bunkyo, Tokyo, Japan; Garvan Institute of Medical Research, Darlinghurst, Sydney, Australia; "Xiangya Hospital Central South University, Changsha, Hunan, China; "Harbin Medical University Cancer Hospital, Harbin, China: Hospital Amau Villanova, Valencia, Spain; National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; "Ell Lily and Company, Indianapolis, USA: **Institut Curie, Paris, France This presentation - The interfictual property or the authoripresenter Contact haverik@msk.co org for permission 0 report and/or distribute ANTONIO FAST CANCER
[Slide 1] ev ERA Breast Cancer INV-PFS and interim OS in patients without ESR1m detected (exploratory analysis) INV-PFS Interim OS 100 100 Giredestrant SOC ET + + everolimus everolimus n 81 n 85 Events, (%) 63 (77.8) 74 (87.1) 80 5.72 5.52 80 Median, mo (95% CI) (5.45, 7.98) (3.88, 6.51) Stratified HR 0.84 (0.59, 1.18) + (95% CI) 60 60 INV-PFS (%) os (%) 40 40 Giredestrant SOC ET : + everolimus everolimus n 81 85 20 20 Events, n (%) 21 (25.9) 27 (31.8) NE NE Median, mo (95% CI) (NE, NE) (27.01, NE) Stratified HR 0.79 (0.44, 1.40) 0 0 (95% CI) 0 3 6 9 12 15 18 21 24 27 30 0 3 6 9 12 15 18 21 24 27 30 33 36 No. at risk Time (mo) No. at risk Time (mo) Giredestrant everolimus 81 64 34 27 19 16 8 1 1 1 Giredestrant everolimus 81 78 74 71 70 66 56 28 14 3 SOC ET everolimus 85 64 33 25 17 12 6 2 2 1 SOC ET everolimus 85 80 74 69 65 59 49 28 16 6 1 --- [Slide 2] TO July by was giredestrant+ everollmus) and mo (SOC everollmus); strawned nn, 0.34, CI, confidence interval; ESR1m, ESR1 mutation; HR, hazard ratio; INV. investigator-assessed; mo, months; PFS, progression-free survival; SOC ET, standard of care endocrine therapy. Presented by: Erica L. Mayer, MD. MPH. BERLIN Content of this presentation is copyright and responsibility of the author. Permission is required for re-use. 2025 ev ERA Breast Cancer Co-primary endpoint - INV-PFS in the ESR1m population Giredestrant + SOC ET + everolimus everolimus n = 102 n = 105 100 Events, n (%) 63 (61.8) 89 (84.8) 80 Median, mo (95% CI) 9.99 (8.08, 12.94) 5.45 (3.75, 5.62) 66.1% Stratified HR 0.38 INV-PFS (%) 60 (95% CI) (0.27, 0.54); p < 0.0001 40.5% 38.1% 40 Exploratory analysis: INV-PFS by SOC ET Total, n Unstratified HR (95% CI) 20 15.2% Exemestane 67 0.40 (0.28, 0.58) Fulvestrant 31 0.44 (0.28, 0.69) 0.2 1.0 5.0 0 Giredestrant SOC ET 0 3 6 9 12 15 18 21 24 27 30 + everolimus better + everolimus better No. at risk Time (mo) Giredestrant everolimus 102 85 61 52 28 13 6 2 2 SOC ET everolimus 105 67 35 25 10 2 1 1 1 Combination therapy with giredestrant + everolimus led to a clinically meaningful 62% reduction in the risk of progression or death in patients with ESR1m Data cutoff: 16 July 2025. PFS by blinded independent radiologist was similar to INV-PFS: Median PFS was 11.14 mo (giredestrant everolimus) and 5.68 mo (SOC ET everolimus); stratified HR, 0.49; 95% CI: 0.34, 0.71. CI, confidence interval; ESR1m. ESR1 mutation: HR. hazard ratio; INV. investigator-assessed; mo, months; PFS, progression-free survival; SOC ET, standard of care endocrine therapy. Presented by: Erica L. Mayer, MD. MPH. congress BERLIN Content of this presentation is copyright and responsibility of the author. Permission is required for re-use. 2025 ESMO --- [Slide 3] ev ERA Breast Cancer Study design A global, randomised, open-label, Phase III trial Enrolment period: August 2022 to October 2024 Key eligibility criteria* N : 373* ER+, HER2- aBC (1-3L of therapy) Giredestrant (30 mg) + everolimus (10 mg)+ Until PD $2 prior lines of ET in the aBC setting R or PD or relapse during/post-CDK4/6i + ET 1:1 unacceptable No prior chemotherapy in the aBC setting SOC ET: : everolimus (10 mg)t toxicity Measurable disease per RECIST v1.1 or evaluable Examestane/ulvestantanden bone metastases 1 Dexamethasone mouthwash prophylaxis and treatment was strongly recommended per SWISH trial protocol Trial was enriched to 55% of patients with ESRim at baseline (centrally tested a circulating fumour DNA) Stratification factors Co-primary endpoints (RECIST v1.1) Prior treatment with fulvestrant (yes VS no) INV-PFS in patients whose tumours had ESR1m ESR1m (yes VS no/indeterminate) INV-PFS in the ITT population Site of disease (visceral [lung and/or Key secondary endpoints liver involvement] VS non-visceral) OS ESMD congress INV-assessed ORR, DoR IN CiricalTials pr number, NC705306340 Adapted ton Mayor EL, at at SABCS 2022 (poster 072-01-07) with permission NL in 0 that int a6C advanced treat cancer, COKAS cyclin-dependent know 46 inhibitor, DoR, duration of esponse ER+, oestrogen receptor positive ESRim, ESR1 mutation ET endocrine therapy HER2-, HER2 negative; NY everythe assessed ITI, intention I took, CAR objective response ale 05, overal survial PD, progressive disease, PFS progression the survival, R randomisation, RECIST, Response Evaluation Criteria in Solid Tumours; SOC ET standard If an entitine therapy 1 Ruge 15, R Lancel Crostigy 2017, 18:654-662 Presented by Erica L Mayer, MD, MPH. Content of his presentation is copyright and responsibility of the author. Permission is required for re-use, BERN ESMO congress
[Slide 1] Pushing beyond the 6-month PFS ceiling after CDK4/6 inhibitors Combination of SERDs/SERMs with targeted therapies including Pl3Ki and CDK4/6i represents the future of ET-based treatment in CDK4/6i-pretreated population ESR1-mut 10 ITT 8 ITT AKT-altered 6 4 2 0 Fulv + Imlun + Fulv + Fulv + SoC + Gired + Fulv + SoC Elac Fulv Cami75 Cami150 SoC Imlun Fulv Fulv Fulv Gedatol + Abema Capi Ipatasertib Everolimus Everolimus Gedatol Palbo EMERALD SERENA-2 EMBER-3 Capitello-291 FINER evERA VIKTORIA-1 ESR1mut only Prior CDK4/6is (ESR1mut + wt) Prior CDK4/6is (ESR1mut + wt) Prior CDK4/6is (AKT altered+ wt) 100% previous CDK4/6is 100% previous CDK4/6is PIK3CA wt 100% previous CDK4/6is "25% 1 CT line for ABC No CT for ABC ~25% 1 CT line for ABC No prior CT for ABC 100% previous CDK4/6is 28% 1 CT line for ABC No prior CT for ABC A. Gennari Bardia A et al SBACS 2021; Bidard FC et al JCO 2022; Oliveira M et al Lancet Oncol Content of this presentation is copyright and responsibility of the author. Permission is required for re-use congress BERLIN 2024; Jhaveri et al SABCS 2024 & NEJM 2024; Turner NC et al NEJM 2023; Chia S 2025 ESMO et al ASCO 2025; Mayer E et al ESMO 2025; Hurvitz S et al ESMO 2025
Highest-engagement tweets about this trial, ranked by KOL discussant count (replies + quote-tweets). Replies in green, quote-tweets in blue. Wall Street, stock-promo, and non-substantive replies excluded.
#ESMO25 Managing HR+/HER2– mBC in 2025 💬An update is likely following the evERA and VIKTORIA-1 trials From Dr. William Gradishar's presentation👇 https://t.co/noV6ro3VPZ
If both ESR1 and Pik3ca is present ?
I couldn’t agree. What is the role of a clinical trial as significant as SONIA ?
This isn't just a treatment flowchart. It is a photograph of a scientific revolution, captured in a single, beautiful, and terrifyingly complex slide. It is the visual proof that the war against cancer is no longer a s
https://t.co/mN7brG6kZJ
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A lot was covered but summary of 7 main studies we touched on during Metastatic HR+ #BreastCancer #SABCS highlights w/ @hoperugo: ✅ #AMBRE ✅ #MONALEESA ✅ #VIKTORIA1 ✅ #SERENA6 ✅ #evERA ✅ #EMBER3 ✅ #ASCENT07 @OncoAlert @OncUpdates #bcsm #OncTwitter https://t.co/rhXigqBzmk
Informative
Major studies at a glance! 📊 These 7 studies from Major Research at a Glance provide crucial evidence-based insights for metastatic HR+ breast cancer—well worth repeated review and discussion.
https://t.co/mN7brG6SPh
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#SABCS2025 Honored to present this exciting data. Efficacy seen regardless of mESR1 or mPIK3CA with ela+eve. Data immature for abema. EVERA also shows benefit with giredestrant/EVE across mESR1 as did EMBER3. @OncoAlert https://t.co/5rErhPB9sK
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Metastatic HR+ #BreastCancer #SABCS highlights w/ @hoperugo: ✅ #AMBRE ✅ #MONALEESA ✅ #VIKTORIA1 ✅ #SERENA6 ✅ #evERA ✅ #EMBER3 ✅ #ASCENT07 Full Discussion: ⭐️ https://t.co/13d2vTlika ⭐️ “Oncology Brothers” podcast #OncTwitter #bcsm @OncoAlert @OncUpdates https://t.co/GD
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#ESMO25 EVeRa (Phase III): Giredestrant + everolimus doubled PFS vs SOC ET + everolimus post-CDK4/6 in HR+/HER2– MBC ESR1 mut population; 10 mo vs 5.4 mo in ESR1-mut tumors. No major benefit in ESR1-WT sub-analysis. https://t.co/q0GN5w38US
+4evERA Breast Cancer is a Phase III randomized open-label trial from Roche evaluating giredestrant — an investigational oral selective estrogen receptor degrader (SERD) — combined with everolimus versus physician's choice endocrine therapy plus everolimus, in patients with ER+/HER2- advanced breast cancer who progressed after a CDK4/6 inhibitor. The trial met its co-primary endpoints at ESMO 2025, with significant PFS benefit in both the ITT and ESR1-mutated populations. Updated subgroup and PRO data were presented at SABCS 2025 and ESMO Breast 2026.
Population: Adults with ER+/HER2- locally advanced or metastatic breast cancer previously treated with a CDK4/6 inhibitor plus endocrine therapy. ESR1-mutation enriched cohort built into co-primary analysis.
Interventions: Giredestrant (oral SERD) + everolimus 10 mg daily versus physician's choice endocrine therapy + everolimus 10 mg daily. Patients continue until progression or unacceptable toxicity.
Endpoints: Co-primary: investigator-assessed PFS in the ITT and ESR1-mutated populations. Secondary: OS, ORR, DoR, CBR, safety, and patient-reported outcomes.
ITT median PFS 8.77 vs 5.49 months (HR 0.56; 95% CI 0.44-0.71; p<0.0001); ESR1-mutated PFS 9.99 vs 5.45 months (HR 0.38; 95% CI 0.27-0.54; p<0.0001). OS immature with positive early trend (ITT HR 0.69; ESR1-mut HR 0.62). ORR improved in both ESR1-mutated and ESR1-wildtype subgroups.
Giredestrant + everolimus was well tolerated with no new safety signals. Notably no photopsia — a class effect seen with some other oral SERDs. The stomatitis profile reflects the everolimus backbone; the ESMO Breast 2026 PRO update emphasized prophylactic dexamethasone mouth rinse as a practical mitigation.
Erika Hamilton flagged the central interpretive tension: “No benefit among those patients WITHOUT ESR1m. Although ITT was significant with high % of pts with ESR1m, benefit is NOT in all-comers.” Hope Rugo — on the discussant side of the ESMO 2025 presentation by Erica Mayer (@elmayermd) — described it as “very nice data from EVERA combining giredestrant/everolimus vs SOC ET/everolimus with marked improvement in PFS and ORR in mESR1 and ITT. ORR also better in ESR1 wt. No added toxicity. Great new and effective Rx combination,” and at SABCS25 added a biomarker caveat: “Note PFS in non ESR1m subgroup similar. ORR better.” Sarah Sammons summarized the topline: “Giredestrant + everolimus doubled PFS vs SOC ET + everolimus post-CDK4/6 in HR+/HER2– MBC ESR1 mut population; 10 mo vs 5.4 mo in ESR1-mut tumors. No major benefit in ESR1-WT sub-analysis.” Virginia Kaklamani placed evERA next to EMBER-3: “Ember 3 updated results. Imlu maintaining benefit. Combo benefit similar to evera trial although here benefit regardless of esr1m. Would love to see the combo approved.” Luca Recco noted the subgroup picture from SABCS25: “Giredestrant + eve confirm consistent PFS benefit across genomic and clinical subgroups in evERA, particularly: PI3K-pathway alterations (PIK3CA, AKT1, PTEN).” Abi Siva flagged the practical safety detail from the PRO update at ESMO Breast 2026: “Dex mouth rinse was recommended to all patients,” addressing the stomatitis class effect.