Phase III German preoperative gemcitabine ± taxane in HER2- early breast cancer. GT vs AT not superior; G alone failed non-inferiority.
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Trial slides shared by KOLs at ESMO Breast 2026 (#ESMOBreast26). Click any image to expand. OCR text extracted via AWS Textract.
[Slide 1] 2026 ESMO BREAST CANCER Annual Congress SERD therapy demonstrates robust anti-proliferative activity in young patients with ER-positive/HER2- negative early breast cancer #ESMODailyReporter ESMO daily REPORTER
[Slide 1] ETOP-IBCSG IBCSG 67-22 PREcoopERA Study Foundation for International Lung & Breast Cancer Research A randomized, multicenter, open-label, window-of-opportunity (WOO) trial for premenopausal patients with ER+/HER2- operable invasive breast cancer 231 Patients randomized Jan'24-Jun'25 at 33 centers in 6 countries Screening WOO Treatment Phase (28 days) 204 patients comprised the primary analysis set Day 29 (13 days) 80, 82 and 42 patients had been assigned to G, 93 Giredestrant (30 mg daily, PO) G+T and A+T, respectively. Paired Ki67 biopsies, received adequate* treatment, Diagnostic biopsy Premenopausal patients with N=231 ER+/HER2-, treatment naive Giredestrant (30 mg daily, PO) R Ki67 a10% (local testing) Re-biopsy / surgery centrally-confirmed pre-treatment tumor in early breast cancer 92 Stage 1, II or operable III Triptorelin (3.75 mg IM, on day 1)2 diagnostic biopsy had Ki67>10%, ER+/HER2- 2:2:1 Anastrozole (1 mg daily, PO) 46 Randomization stratified Triptorelin (3.75 mg IM, on day 1)2 226 patients comprised the safety analysis set - Ki67 (10%-19 vs >20%, per local assessment) who initiated WOO treatment - Age ($40 vs >40 years) Day 1 Day 15 Day 28 FFPE Blood Blood Blood FFPE I I Ki67 Ki67 KJ67 of tumor biopsies centrally assessed at IBCSG Central Pathology Office for primary analysis 1 Oral treatment (giredestrant or anastrozole) is given from day until the day of re-biopsy/surgery 7 If re-biopsy/surgery cannot be done on day 29 (13 days) from first injection, a second triptorelin injection should be given on day 29 (13 days). "Adequate treatment is >14 days of oral ET until within 3 days of biopsy/surgery and 2nd triptorelin received if needed (if re biopsy/surgery delayed), as pre-specified in the protocol Of 204 patients, 194 had the re-biopsy/surgery procedure at 29+/-3 days and the 10 others were at 20,23,33(n=5),36(n=2) or 42 days with continued treatment Abbreviations: ER=estrogen receptor, SERD=selective ER degrader; FFPE=formalin-fixed paraffin-embedded; R=randomization; PO=by mouth; IM=intramuscular ESMO Content of this presentation is copyright and responsibility of the author, Elisabetta Munzone, MD. Permission is required for re-use --- [Slide 2] ETOP-IBCSG Conclusions Foundation for International Lung & Breast Cancer Research Giredestrant plus triptorelin achieved the greatest anti-proliferative effect, with Ki67 reduction of -79.6% vs. -73.7% for anastrozole plus triptorelin, not statistically significant (p = 0.18) Giredestrant with a -68.2% reduction in Ki67 did not meet non-inferiority vs. giredestrant + triptorelin, the difference on the log scale was 0.45 (95% CI 0.22-0.67), exceeding the pre-specified margin of 0.40. Correlation between ER degradation and Ki67 reduction (r = 0.40) supports on-target activity of giredestrant Age contributed to variability of anti-proliferative effect In older premenopausal patients deeper Ki67 suppression with giredestrant alone was observed Analyses exploring the relationship between hormonal levels and correlation with proliferation dynamics are ongoing Giredestrant is biologically active in premenopausal women with or without triptorelin ESMO Content of this presentation is copyright and responsibility of the author, Elisabetta Munzone, MD. Permission is required for re-use --- [Slide 3] ETOP-IBCSG Pre- and Post-WOO treatment Ki67 and CCCA Foundation for International Lung & Breast Cancer Research 80.0 Mean pre-treatment Ki67 was 21.7% 60.0 20.1% of patients overall had CCCA Ki67 (%) 40.0 : G G+T A+T 20.0 N in 1° analysis set 80 82 42 % of patients (95% CI) 10.0 1 Post Ki67 â 10% 62.5% (51.0-73.1) 86.6% (77.3-93.1) 76.2% (60.6-88.0) 2.7 Post Ki67 S 2.7% 12.5% (6.2-21.8) 26.8% (17.6-37.8) 21.4% (10.3-36.8) 0.0 Pre Post Pre Post Pre Post G G+T A+T K167 Pre Post Pre Post Pre Post Geometric mean 22.0 7.0 21.9 4.5 20.6 5.3 (95% CI) (20.2-24.0) (5.8-8.5) (19.6-24.6) (3.9-5.2) (18.1-23.4) (4.1-6.8) Pre and post WOO treatment Ki67 values were summarized descriptively as geometric means. Abbreviations CCCA=complete cell cycle arrest (K67s2.7%); Cl=confidence interval ESMO Content of this presentation is copyright and responsibility of the author, Elisabetta Munzone, MD. Permission is required for re-use --- [Slide 4] ETOP-IBCSG Primary Endpoint Results: Foundation for International Lung & Breast Cancer Research After 4 weeks, Ki67 was substantially reduced by all 3 regimens 60 40 20 Ki67 percentage change (%) 0 -20 -40 -60 -80 -100 Giredestrant Giredestrant triptorelin Anastrozole + triptorelin G G+T A+T N in 1° analysis set 80 82 42 Geometric mean %change Ki67 -68.2% -79.6% -73.7% 95% CI (-73.3% to -62.2%) (-82.4% to -76.4%) (79.3% to -66.6%) Not non-inferior to G+T Not superior to A+T (p=0.18) Analysis used ANCOVA of centrally-assessed post-treatment Ki67 (log scale), with centrally-assessed pre-treatment Ki67 and treatment assignment as covariates. For the superiority comparison of G+T vs A+T, the parameter estimate was (=0.19; 95%CI -0.47 to 0.09) corresponding to a geometric mean ratio of 0.83 For the non-inferiority comparison of G vs G+T, the parameter estimate was 0.45 (95% CI 0.22 to 0.67) which exceeded the non-inferiority boundary of 0.40 ESMO Content of this presentation is copyright and responsibility of the author, Elisabetta Munzone, MD. Permission is required for re-use
[Slide 1] ADDITIONAL QUESTIONS Only one month of OFS may not be adequate exposure to achieve postmenopausal state in younger patients. Is steady state achieved? Are comparisons accurate? Is Ki67 endpoint sensitive enough to discriminate between effective therapies in WOO? Should other biomarkers of response be used (gene expression assays, ctDNA dynamics)? Is ET monotherapy best option in this setting, or should ET be combined with a targeted agent? PREcoopERA does not support omission of OFS with oral SERD when optimizing activity: What are next steps to determine ability to potentially defer OFS, and in whom? Erica L. Mayer MD, MPH Content of this presentation is copyright and responsibility of the author. Permission is required for re-use ESMO
[Slide 1] Trial Everyone Is Talking About at ESMO Breast 2026 MV MV Onco PRECOOPERA WOO WOO WOO WOO! WOO WOO! WOO! WOO WOO! COPPER LET'S UNDERSTAND THE FULL FORM PRE- COOP Premenopausal Cooperative Group ERA- WOO Estrogen Receptor Window of Antagonist Opportunity
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.
PREcoopERA WOO trial: neoadjuvant giredestrant alone (4 wks) was NOT non-inferior to giredestr+OFS in suppressing Ki67, suggesting that OFS adds efficacy to giredestrant in premenopausal pts. OFS+gire was numerically, but not statistically better than OFS+AI at suppressing Ki67.
#ESMOBreast26: Giredestrant, a novel SERD, showed robust anti-proliferative activity in premenopausal patients with stage I–III ER-positive/HER2-negative #BreastCancer in the PREcoopERA trial, as demonstrated by reduction in Ki67. #ESMODailyReporter 🔗 https://t.co/a44uZAMl17 htt
PREcoopERA is a 28-day Phase II window-of-opportunity randomized trial evaluating whether the oral SERD giredestrant — alone or with the LHRH analogue triptorelin — can effectively reduce tumour proliferation (Ki67) in premenopausal patients with untreated ER-positive, HER2-negative early breast cancer compared to anastrozole + triptorelin. Presented at ESMO Breast Cancer 2026 as LBA2. The trial tested two hypotheses: (1) giredestrant + triptorelin superior to anastrozole + triptorelin; (2) giredestrant alone non-inferior to giredestrant + triptorelin.
Population: Premenopausal patients with untreated ER-positive (Allred ≥6/8), HER2-negative, Stage I–III invasive early breast cancer with baseline Ki67 >10%. Pre-treatment Ki67 mean 21.7%.
Interventions: Giredestrant 30 mg/day PO ± triptorelin 3.75 mg IM every 28 days, or anastrozole 1 mg/day PO + triptorelin 3.75 mg IM every 28 days. Treatment duration: 28 days then surgery.
Endpoints: Primary: centrally-assessed change in Ki67 between baseline biopsy and surgery. Tested for superiority (GT vs AT) and non-inferiority (G vs GT, margin log 0.40).
All three arms produced robust Ki67 reductions: GT −79.6% (95% CI −82.4 to −76.4); AT −73.7% (−79.3 to −66.6); G alone −68.2% (−73.3 to −62.2). Superiority comparison GT vs AT did not reach significance (log difference −0.19, 95% CI −0.47 to 0.09; p=0.18). Giredestrant alone did NOT meet non-inferiority vs GT (log difference 0.45, exceeding the 0.40 margin). Deeper Ki67 suppression: ≤10% post-treatment in 86.6% (GT) vs 76.2% (AT) vs 62.5% (G); ≤2.7% in 26.8% / 21.4% / 12.5%.
Treatment was generally well tolerated. Grade 3 adverse events: 2.2% (GT), 4.4% (G), 4.4% (AT). No grade 4 or 5 events. Two patients in the giredestrant monotherapy arm developed ovarian cysts. Although safety was favourable across arms, the trial does NOT support an OFS-free approach: giredestrant alone did not meet non-inferiority vs giredestrant + triptorelin for Ki67 suppression, reaffirming that ovarian function suppression remains important for optimal anti-proliferative effect in premenopausal patients.
Paolo Tarantino summarized PREcoopERA as a window-of-opportunity readout in which “neoadjuvant giredestrant alone (4 wks) was NOT non-inferior to giredestr+OFS in suppressing Ki67, suggesting that OFS adds efficacy to giredestrant in premenopausal pts.” He noted further that “OFS+gire was numerically, but not statistically better than OFS+AI at suppressing Ki67.” The OCR-captured conclusion slide reinforced the on-target activity claim, noting “Giredestrant is biologically active in premenopausal women with or without triptorelin,” while the difference between giredestrant alone and giredestrant+triptorelin exceeded the pre-specified non-inferiority margin. Dana-Farber’s Breast Oncology Center flagged that Erica Mayer’s discussion paired PREcoopERA with TRAK-ER, and Mayer’s conclusion slide (captured in OCR) cautioned that “oral SERDs should only be used with OFS in premenopausal patients” pending more data on prolonged SERD monotherapy.
| Handle | Name | Sentiment | Tweet (excerpt) | Imp. |
|---|---|---|---|---|
| @myESMO | ESMO - Eur. Oncology | Neutral | #ESMOBreast26: Giredestrant, a novel SERD, showed robust anti-proliferative activity in premenopausal patients with stag… | 1,183 |
| @PTarantinoMD | Paolo Tarantino | Neutral | PREcoopERA WOO trial: neoadjuvant giredestrant alone (4 wks) was NOT non-inferior to giredestr+OFS in suppressing Ki67, … | 561 |
| @PTarantinoMD | Paolo Tarantino | Neutral | @elmayermd: PREcoopERA does not support omission of OFS with oral SERDs when optimizing activity. https://t.co/9lo62PDST… | 360 |
| @ChandrakanthMv | MV Chandrakanth | Neutral | “PRECOOPERA WOO” may be one of the most discussed trial names at #ESMOBreast2026 😄 But what does it actually mean? Here’… | 237 |
