Final results of TALENT: A neoadjuvant trial of T-DXd with or without anastrozole, or in sequence with chemotherapy for HER2-low, HR+ early-stage breast cancer
https://esmocongress.esmo.org
ESMO Congress 2026
October 23–27, 2026 · Madrid · 2669 items
TALENT
★★★Late-breaking33 people · 36 posts · 1 abstract
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T-DXd (trastuzumab deruxtecan) belongs to the anti-HER2 antibody-drug conjugate (ADC) class. As for the evidence already established for this asset, the usable information in the current materials comes from the on-site discussants: several experts used T-DXd's success in the metastatic breast cancer setting as the reference background, and debated from there whether that benefit can be extrapolated to early-stage disease. Regarding key published phase III trials of ADCs in the same class, the background references provided this time all belong to other fields such as psychology, statistical methodology, and sports science, containing no anti-HER2 ADC or breast cancer trial data; such prior evidence is pending confirmation in these materials and is therefore not elaborated here.
At ESMO26, Sara Hurvitz presented the final results of the TALENT trial (LBA23): three neoadjuvant strategies in HR+/HER2-low early breast cancer — T-DXd alone (6-8 cycles), T-DXd plus anastrozole, and T-DXd x 4 cycles followed by sequential TC chemotherapy x 4. The key numbers: pCR was 7%, 3%, and 9%, respectively; RCB 0/1 was 16%, 17%, and 17%, respectively. Despite an overall response rate (ORR) of about 66%, pCR remained very low, and per the live posts, there were no pCRs without 8 cycles. The authors concluded the benefit was "modest," while one commenter called it "disappointing." Another post noted that higher baseline HER2 protein levels may be associated with higher pCR rates.
Relative to prior knowledge, the step TALENT advances lies in answering three questions: first, adding endocrine therapy (anastrozole) to T-DXd did not improve pCR (3% vs 7% for monotherapy); second, sequencing TC chemotherapy brought only marginal improvement (9%); third, the contrast between high ORR and low pCR again confirms that pCR is a limited surrogate endpoint in HR+ disease, a point emphasized by multiple discussants. In the discussion session, Barbara Pistilli placed TALENT in the context of three trials of ADCs sharing the same target, linker and payload class, noting that its low pCR rate is comparable to NACT and other ADCs in HR+/HER2- early breast cancer. Some on-site commentary called this "probably first negative trial" for T-DXd, but sample size and statistical design details were not disclosed in the posts, so that characterization awaits confirmation.
As for limitations, the materials here are only live conference posts, with no sample size, study design, or survival follow-up data disclosed; on safety, discussants explicitly raised the need to weigh efficacy, ILD risk, and treatment positioning in early disease, but specific safety figures were not given in the posts. Given the inherent heterogeneity of HER2-low disease, the overall judgment from attendees is that these results do not support T-DXd as an alternative to standard neoadjuvant chemotherapy in HR+/HER2-low early breast cancer, and whether it can move from metastatic benefit to curative-intent early treatment still requires more evidence.
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Yakup Ergün@dr_yakupergun Dr Amol Akhade@SuyogCancer Sara Tolaney@stolaney1 TALENT trial presented by Sara Hurvitz: Preop TDXd in HR+ HER2-low breast cancer
Matteo Lambertini, MD PhD@matteolambe ★★★Same topic TALENT · 33 peopletrastuzumabderuxtecanHER2#BREASTCANCER#TRASTUZUMABDERUXTECAN542 views20 likes10 reposts0 repliesStephanie Graff, MD, FACP, FASCO@DrSGraff TALENT—neoadj TDXd (6-8 cycles) +/- AI in HER2 low HR+ early stage breast ca
Mustafa Özdoğan, MD@ozdogan_md Can an ADC move from metastatic benefit into curative-intent early breast cancer?
Erika Hamilton, MD, FASCO@ErikaHamilton9 TALENT- neoadj T-DXd in HR+/HER2-low #bcsm
ESMO - Eur. Oncology@myESMO ★★★Same topic TALENT · 33 peopletrastuzumabderuxtecanHER2#CLINICALTRIAL#EARLYBREASTCANCER#INSIGHTSBYESMO1298 views9 likes6 reposts0 repliesGaia Griguolo@GaiaGriguolo Yakup Ergün@dr_yakupergun In TALENT, adding anastrozole did not increase pCR.
引用@#ESMO26 | TALENT Neoadjuvant T-DXd showed very low pCR rates in HR+/HER2-low early breast cancer: - T-DXd: 7% - T-DXd + anastrozole: 3% - T-DXd → chemotherapy: 9% We should remember that pCR is a limited surrogate endpoint in HR+ disease. However, these results do not support T-DXd as an alternative to standard neoadjuvant chemotherapy. Moreover, given the heterogeneity of HER2-low disease, I find it unsurprising that the success of T-DXd in the metastatic setting does not translate into similar outcomes in early-stage disease, despite the lower tumor burden.
Philippe Aftimos, MD @aftimosp Some take-away points from @BarbaraPistill2 ‘s dicussion of the anti-HER2 ADCs abstracts
Kazuki Nozawa, MD@kazuki_nozawa Ahmed Alanazi | أحمد العنزي@alanazi002 Carmen Criscitiello@CarmenCriscit Armando Orlandi@ArmandOrlandi Cowabunga! 🌊 Riding the Breast Cancer Wave 🏄🏻♂️🤙🏻 from #ESMO26
Kristina Jankovic, MD@JankovicK Yakup Ergün@dr_yakupergun 引用@#ESMO26 | TALENT Neoadjuvant T-DXd showed very low pCR rates in HR+/HER2-low early breast cancer: - T-DXd: 7% - T-DXd + anastrozole: 3% - T-DXd → chemotherapy: 9% We should remember that pCR is a limited surrogate endpoint in HR+ disease. However, these results do not support T-DXd as an alternative to standard neoadjuvant chemotherapy. Moreover, given the heterogeneity of HER2-low disease, I find it unsurprising that the success of T-DXd in the metastatic setting does not translate into similar outcomes in early-stage disease, despite the lower tumor burden.
Dr Rishabh Jain@DrRishabhOnco 引用@🚨 ESMO 2026 | TOP 15 BREAST CANCER TRIALS TO WATCH! 🎗️ Breast cancer takes center stage at #ESMO26! From selective CDK4 inhibition and next-generation ADCs to immunotherapy, treatment sequencing, and long-term survival updates, these are the 15 studies I’m watching most closely. 👇 🔴 HR+/HER2− BREAST CANCER 1️⃣ FOURLIGHT-1: Can selective CDK4 inhibition with atirmociclib + fulvestrant improve outcomes in second-line metastatic disease? 2️⃣ PANKU-Breast01: Can the EGFR×HER3 bispecific ADC izalontamab brengitecan outperform standard chemotherapy? 3️⃣ KEYNOTE-B49: Could pembrolizumab + chemotherapy establish a role for immunotherapy in PD-L1+ HR+/HER2− metastatic breast cancer? 4️⃣ NATALEE: Will the 6-year follow-up strengthen the case for adjuvant ribociclib in early breast cancer? 5️⃣ FINER / MA.40: Does ipatasertib + fulvestrant deliver an overall survival benefit after CDK4/6 inhibitor exposure? 6️⃣ NSABP B-42: What do the final long-term results tell us about extended adjuvant aromatase inhibitor therapy? 7️⃣ TALENT: Can neoadjuvant T-DXd sequencing with chemotherapy improve outcomes in HR+/HER2-low early breast cancer? 8️⃣ SWITCH: Can switching ADC targets while retaining a TOP1 inhibitor payload overcome resistance to prior ADC treatment? 🔵 HER2-POSITIVE / HER2-LOW BREAST CANCER 9️⃣ BRIDGET: Can tucatinib-based treatment improve disease control after isolated progression in HER2+ metastatic breast cancer? 🔟 DESTINY-Breast09: What do the CNS analyses reveal about first-line T-DXd + pertuzumab in HER2+ metastatic disease? 1️⃣1️⃣ HORIZON-Breast06: Can trastuzumab rezetecan establish a new treatment option in HER2-low metastatic breast cancer? 1️⃣2️⃣ APEX-Breast01: Could another novel TOP1 ADC challenge standard chemotherapy in HER2-low disease? 🟢 TRIPLE-NEGATIVE BREAST CANCER 1️⃣3️⃣ TROPION-Breast02: What do the CNS outcomes reveal about datopotamab deruxtecan in metastatic TNBC? 1️⃣4️⃣ POP-DURVA: Can short-course neoadjuvant durvalumab produce meaningful pathological responses in selected stage I TNBC? 1️⃣5️⃣ OptiTROP-Breast01: Will the final overall survival analysis strengthen the evidence for sacituzumab tirumotecan in metastatic TNBC? 🔬 ALSO ON MY RADAR VIKTORIA-1, postMONARCH, lidERA, DESTINY-Breast05, GIM3 FATA, MRD studies and CHARISMA. 🔥 THREE BIG QUESTIONS FOR ESMO 2026 🔹 Will next-generation ADCs redefine treatment sequencing? 🔹 Can immunotherapy and selective CDK4 inhibition expand therapeutic options in HR-positive disease? 🔹 Will mature survival and CNS outcomes change clinical practice? 📌 This is a pre-congress watchlist ranked and grouped for clinical relevance, not a summary of established positive results. Which breast cancer trial are you most excited about, and which has the greatest potential to change your practice? 👇 @myesmo @ESMO_open @ASCO @oncoalert #ESMO26 #BreastCancer #Oncology #ClinicalTrials
Philippe Aftimos, MD @aftimosp 引用@#ESMO26: Final results from the TALENT #ClinicalTrial show low pathological complete response rates with the antibody–drug conjugate (#ADC) trastuzumab deruxtecan in HR-positive, HER2-low #EarlyBreastCancer, as discussed by @breastDoktor #InsightsbyESMO ➡️ https://ow.ly/ZBwi50ZZXLm
Oncoinfo@Oncoinfo_it KOL Pulse AI@KolPulseAI "Author concludes “modest” benefit; I would say “disappointing”." @DrSGraff
ScienceLink@sciencelinkonco #ScienceLink #Madrid2026 #ESMO26 #TALENT #Trastuzumabderuxtecán
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