TALENT: Neoadjuvant T-DXd pCR 3-9% in HR+/HER2-Low EBC (ESMO 2026)

Q: What is the TALENT trial?

TALENT (TRIO-US B-12; NCT04553770) is a phase 2, two-stage neoadjuvant trial in operable, previously untreated HR-positive, HER2-low (IHC 1+ or 2+, ISH non-amplified) stage II-III breast cancer. Patients were randomized 1:1 to trastuzumab deruxtecan 5.4 mg/kg every 3 weeks alone (Arm A) or with anastrozole (Arm B), for 6 cycles and, after an amendment once 29 patients were enrolled, 8 cycles. A third arm (Arm C) then gave 4 cycles of T-DXd followed by 4 cycles of docetaxel plus cyclophosphamide (TC). 132 patients were enrolled from November 2020 to February 2026. The lead sponsor is UCLA's Jonsson Comprehensive Cancer Center with Translational Research in Oncology (TRIO-US); funding came from Daiichi Sankyo.

Q: What did TALENT show at ESMO 2026?

Pathologic complete response (RCB0) rates were low: 7% (3/45) with T-DXd alone, 3% (1/29) with T-DXd plus anastrozole and 9% (5/58) with T-DXd followed by TC. pCR or near-pCR (RCB0/1) was 16%, 17% and 17%. Tumors still shrank: on the presentation slides ORR was 62%, 66% and 72% in all treated patients; the abstract reports 67%, 66% and 65% in evaluable patients. The investigators concluded that neoadjuvant T-DXd showed modest activity, that anastrozole did not improve pCR and that sequencing with chemotherapy only marginally improved it.

Q: Was TALENT a negative trial?

TALENT is a phase 2 two-stage study; an arm advanced to stage 2 if at least 2 pCRs were seen. The investigators' own conclusion was "modest clinical activity". Several physicians described the result as disappointing or not practice-changing, while others noted that pCR is a limited surrogate in HR-positive disease and that event-free survival is still being analyzed.

Q: Is trastuzumab deruxtecan approved for early-stage HER2-low breast cancer?

No. In HER2-low breast cancer, Enhertu (fam-trastuzumab deruxtecan-nxki) is FDA approved only for unresectable or metastatic disease: after prior chemotherapy (DESTINY-Breast04, August 2022) and, for HR-positive HER2-low or HER2-ultralow disease, after one or more endocrine therapies in the metastatic setting (DESTINY-Breast06, January 2025). Neoadjuvant use as in TALENT is investigational.

Q: What safety signals were reported in TALENT?

On the presentation slides, grade 3 or higher treatment-related adverse events occurred in 24% (Arm A), 17% (Arm B) and 28% (Arm C). There were three cases of grade 2 drug-related ILD/pneumonitis (one in Arm B, two in Arm C) and one treatment-related death (Arm A). Nausea and fatigue were the most common adverse events.

Q: What did the biomarker analyses show?

Median HER2 protein measured by TROPLEX fell during T-DXd treatment, from 707 to 150 amol/mm2 in Arm A and from 778 to 83 amol/mm2 in Arm B (baseline to surgery), while TROP2 stayed relatively stable. Per the abstract, HER2 levels were higher in tumors that reached RCB0 than in those with residual disease, suggesting HER2 level may correlate with response; the investigators note the sample size is small.

Influence Leaders

Top KOLs Discussing TALENT

Physicians posting about the LBA23 results, ranked by views of their TALENT posts. The presenter, Sara A. Hurvitz, MD (Fred Hutch Cancer Center, University of Washington), has no verifiable X account and is not shown.

Philippe Aftimos, MD 

@aftimosp

849 views

Erika Hamilton, MD, FASCO

@ErikaHamilton9

844 views

Mitsuo Terada, MD, PhD@乳腺科医

TALENT trial presented by Sara Hurvitz: Preop TDXd in HR+ HER2-low breast cancer Preop TDXd: 7% TDXd+AI: 3% TDXd-->TC: 9% Adding endocrine therapy and sequencing chemo with TDXd didn't seem to improve pCR @OncoAlert #ESMO2026 https://t.co/dArlOO4Mpa
— Sara Tolaney (@stolaney1) Oct 23, 2026

Conference Presentations

TALENT Key Slides & Visuals

The LBA23 presentation slides (presenter: Sara A. Hurvitz, MD) as shared on X by physicians in the session, followed by the abstract and physician-made infographics. Click any image to view it full size.

Armando Orlandi@ArmandOrlandi

Title, design, pathologic response, conclusions

ESMO 2026 · LBA23 · Oct 23, 2026

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Title slide: Final results of TALENT, presenter Sara A. Hurvitz, MD, Fred Hutch Cancer Center - TALENT, ESMO 2026 LBA23, presenter Sara A. Hurvitz, MD (photo shared by Armando Orlandi)

TALENT addition of third arm slide: Arm C T-DXd x4 followed by docetaxel plus cyclophosphamide (TC) x4, Arm B stopped at stage I - TALENT, ESMO 2026 LBA23, presenter Sara A. Hurvitz, MD (photo shared by Armando Orlandi)

TALENT pathologic response slide: pCR 7% T-DXd, 3% T-DXd plus anastrozole, 9% T-DXd then TC; RCB0/1 16%, 17%, 17% - TALENT, ESMO 2026 LBA23, presenter Sara A. Hurvitz, MD (photo shared by Armando Orlandi)

TALENT conclusions slide: modest activity of neoadjuvant T-DXd; anastrozole did not improve pCR; sequencing with chemotherapy only marginally improved pCR - TALENT, ESMO 2026 LBA23, presenter Sara A. Hurvitz, MD (photo shared by Armando Orlandi)

Pathologic response and ORR, as printed on the LBA23 presentation slides (all treated patients)

Endpoint	Arm A: T-DXd (N=45)	Arm B: T-DXd + anastrozole (N=29)	Arm C: T-DXd → TC (N=58)
pCR (RCB0)	3/45 (7%)	1/29 (3%)	5/58 (9%)
pCR or near-pCR (RCB0/1)	7/45 (16%)	5/29 (17%)	10/58 (17%)
RCB0 / RCB1, 6 cycles	0 / 13% (N=15)	0 / 7% (N=14)	—
RCB0 / RCB1, 8 cycles	10% / 7% (N=30)	7% / 20% (N=15)	9% / 9% (N=58)
ORR (CR / PR)	28/45 (62%) (11% / 51%)	19/29 (66%) (7% / 59%)	42/58 (72%) (16% / 57%)

Slide text (transcribed by KOL Pulse from the slide images) [Image 1] 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. Sara A. Hurvitz, Nicholas P. McAndrew, David Chan, Lisa S. Wang, Vu Phan, Thomas Lomis, Nina M. Lamble, Justin Tiulim, Brian DiCarlo, Deborah Villa, Nihal Abdulla, Giribala Patel, Aashini K. Master, Swati Sikaria, Shaker Dakhil, Vidhya Nair, Michael F. Press, David L. Rimm, Chi-Hong Tseng, Aditya Bardia. Presenting author: Sara A. Hurvitz, MD, Fred Hutch Cancer Center, University of Washington, Seattle, WA, USA. 23 October 2026. --- [Image 2] TALENT: Addition of Third Arm. Stage I: any arm with >=2 pCR pass to Stage II expansion. N=58 randomized 1:1 to Arm A or Arm B. Arm A T-DXd 5.4 mg/kg: passed, enroll additional patients. Arm B T-DXd 5.4 mg/kg + anastrozole (+GnRH analog for men/premenopausal women): STOP. Arm C (N=29) T-DXd x 4 -> TC x 4: enroll additional patients*. *Arm C started enrollment after completion of Arm A/B. pCR: ypT0/is, ypN0. --- [Image 3] Pathologic Response (by arm and cycles). pCR rate: Arm A T-DXd 3/45 = 7%; Arm B T-DXd/anastrozole 1/29 = 3%; Arm C T-DXd->TC 5/58 = 9%. RCB0/1: 7/45 = 16%; 5/29 = 17%; 10/58 = 17%. By cycles, RCB0 / RCB1: Arm A 6 cycles (N=15) 0 / 13%; Arm A 8 cycles (N=30) 10% / 7%; Arm B 6 cycles (N=14) 0 / 7%; Arm B 8 cycles (N=15) 7% / 20%; Arm C 8 cycles (N=58) 9% / 9%. *3 pts with no surgery results enrolled to 8 cycles of treatment (1 withdrew consent; 1 expired; 1 had PD); **2 pts with no surgery results (withdrew consent/loss to follow-up). RCB 0 = pCR. Histology or IHC status did not appear to be associated with RCB response. --- [Image 4] Conclusions. Neoadjuvant T-DXd demonstrated modest clinical activity in HER2 low, HR+ localized breast cancer. Addition of endocrine therapy to T-DXd did not improve pCR rate (pCR rate T-DXd: 7%, T-DXd + anastrozole 3%). Sequencing T-DXd with multiagent chemotherapy only marginally improved pCR rate (pCR rate T-DXd: 7%, T-DXd->TC 9%). Safety: nausea and fatigue were the most common AE; 3 cases of grade 2 ILD; 1 patient death. HER2 protein levels decreased in Arms A&B after treatment with T-DXd. Higher baseline HER2 protein level may be associated with pCR in Arms A&B but sample size is small and data from Arm C are pending. Ongoing analyses include: event free survival; breast conserving surgery rates; biomarkers: ctDNA, whole genome sequencing, intrinsic subtyping, multiplex IHC, RNA seq transcriptomic analyses; patient-reported outcomes; ovarian function.

Yakup Ergün@dr_yakupergun

Biomarker schedule, baseline characteristics, pathologic response

ESMO 2026 · LBA23 · Oct 23, 2026

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TALENT biomarker collection and imaging assessments slide: biopsies at baseline, cycle 1 day 17-21 and surgery; ctDNA; central pathology review - TALENT, ESMO 2026 LBA23, presenter Sara A. Hurvitz, MD (photo shared by Yakup Ergün)

TALENT baseline characteristics slide by arm: median age 57, 55 and 52 years; node-positive 53%, 55% and 81% - TALENT, ESMO 2026 LBA23, presenter Sara A. Hurvitz, MD (photo shared by Yakup Ergün)

Slide text (transcribed by KOL Pulse from the slide images) [Image 1] TALENT: Biomarker Collection & Imaging Assessments. Arm A T-DXd 5.4 mg/kg; Arm B T-DXd 5.4 mg/kg + anastrozole; Arm C T-DXd x 4 -> TC x 4; then surgery. Tumor sample from archival or fresh biopsy at baseline, biopsy between C1D17-C1D21, and tumor sample at surgery. Circulating tumor DNA analysis collected at baseline, C1D1, C2D1 and end of treatment. Tumor imaging performed (ultrasound and mammogram) at baseline and EOT; ultrasound or mammogram at cycle 2 (modality at the discretion of the investigator). All tissue collected for study: pathology centrally reviewed. --- [Image 2] Baseline Characteristics, Arm A (N=45) / Arm B (N=29) / Arm C (N=58). Median age (range): 57 (33-87) / 55 (32-83) / 52 (29-79). Post-menopausal (2 men in Arm A): 28 (62%) / 17 (59%) / 26 (45%). Baseline HER2 (central review) 0: 3 (7%) / 2 (7%) / 0; 1+: 32 (71%) / 25 (86%) / 36 (62%); 2+: 9 (20%) / 2 (7%) / 22 (38%). Invasive ductal 40 (89%) / 26 (90%) / 53 (91%); invasive lobular 5 (11%) / 3 (10%) / 5 (9%). ER+ and PR+ (local review): 39 (87%) / 26 (90%) / 48 (83%). Node positive: 24 (53%) / 16 (55%) / 47 (81%). Stage IB: 0 / 0 / 2 (3%); IIA/IIB: 12 (27%)/20 (44%) / 11 (38%)/15 (52%) / 18 (31%)/25 (43%); IIIA/IIIB/IIIC: 10 (22%)/2 (4%)/1 (2%) / 3 (10%)/0/0 / 8 (14%)/4 (7%)/1 (2%). Footnotes: 1 Arm A patient with 1+ and 2+ (multicentric lesion); baseline HER2 expression was 1+ or 2+ based on local review; 1 patient with mixed ductal/lobular. --- [Image 3] Pathologic Response (by arm and cycles). pCR rate: Arm A T-DXd 3/45 = 7%; Arm B T-DXd/anastrozole 1/29 = 3%; Arm C T-DXd->TC 5/58 = 9%. RCB0/1: 7/45 = 16%; 5/29 = 17%; 10/58 = 17%. By cycles, RCB0 / RCB1: Arm A 6 cycles (N=15) 0 / 13%; Arm A 8 cycles (N=30) 10% / 7%; Arm B 6 cycles (N=14) 0 / 7%; Arm B 8 cycles (N=15) 7% / 20%; Arm C 8 cycles (N=58) 9% / 9%. *3 pts with no surgery results enrolled to 8 cycles of treatment (1 withdrew consent; 1 expired; 1 had PD); **2 pts with no surgery results (withdrew consent/loss to follow-up). RCB 0 = pCR. Histology or IHC status did not appear to be associated with RCB response. --- [Image 4] Conclusions. Neoadjuvant T-DXd demonstrated modest clinical activity in HER2 low, HR+ localized breast cancer. Addition of endocrine therapy to T-DXd did not improve pCR rate (pCR rate T-DXd: 7%, T-DXd + anastrozole 3%). Sequencing T-DXd with multiagent chemotherapy only marginally improved pCR rate (pCR rate T-DXd: 7%, T-DXd->TC 9%). Safety: nausea and fatigue were the most common AE; 3 cases of grade 2 ILD; 1 patient death. HER2 protein levels decreased in Arms A&B after treatment with T-DXd. Higher baseline HER2 protein level may be associated with pCR in Arms A&B but sample size is small and data from Arm C are pending. Ongoing analyses include: event free survival; breast conserving surgery rates; biomarkers: ctDNA, whole genome sequencing, intrinsic subtyping, multiplex IHC, RNA seq transcriptomic analyses; patient-reported outcomes; ovarian function.

Erika Hamilton, MD, FASCO@ErikaHamilton9

Baseline Ki67 and grade, objective response rate

ESMO 2026 · LBA23 · Oct 23, 2026

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TALENT baseline characteristics (continued) slide: central Ki67 and tumor grade by arm - TALENT, ESMO 2026 LBA23, presenter Sara A. Hurvitz, MD (photo shared by Erika Hamilton, MD, FASCO)

TALENT objective response rate slide with waterfall plots: ORR 62% Arm A, 66% Arm B, 72% Arm C (intention-to-treat) - TALENT, ESMO 2026 LBA23, presenter Sara A. Hurvitz, MD (photo shared by Erika Hamilton, MD, FASCO)

Slide text (transcribed by KOL Pulse from the slide images) [Image 1] TALENT: Addition of Third Arm. Stage I: any arm with >=2 pCR pass to Stage II expansion. N=58 randomized 1:1 to Arm A or Arm B. Arm A T-DXd 5.4 mg/kg: passed, enroll additional patients. Arm B T-DXd 5.4 mg/kg + anastrozole (+GnRH analog for men/premenopausal women): STOP. Arm C (N=29) T-DXd x 4 -> TC x 4: enroll additional patients*. *Arm C started enrollment after completion of Arm A/B. pCR: ypT0/is, ypN0. --- [Image 2] Baseline Characteristics (continued), Arm A (N=45) / Arm B (N=29) / Arm C (N=58). Baseline Ki67 (central review) <10%: 2 (4%) / 0 / 8 (14%); >=10% and <30%: 20 (44%) / 10 (34%) / 19 (33%); >=30%: 23 (51%) / 19 (66%) / 31 (53%). Tumor grade (local) grade 1: 4 (9%) / 1 (3%) / 0; grade 2: 22 (49%) / 16 (55%) / 29 (50%); grade 3: 19 (42%) / 11 (38%) / 29 (50%); not reported: 0 / 1 (3%) / 0. --- [Image 3] Objective Response Rate (intention-to-treat). Arm A (T-DXd), N=45: ORR 28/45 = 62%; CR 5/45 = 11%; PR 23/45 = 51%. Arm B (T-DXd + anastrozole), N=29: ORR 19/29 = 66%; CR 2/29 = 7%; PR 17/29 = 59%. Arm C (T-DXd x4 -> TC x4), N=58: ORR 42/58 = 72%; CR 9/58 = 16%; PR 33/58 = 57%. 3 patients did not have EOT imaging, but were included in the ITT denominator for ORR analysis per protocol. Waterfall plot: change in tumor size after treatment vs baseline per RECIST v1.1. --- [Image 4] Pathologic Response (by arm and cycles). pCR rate: Arm A T-DXd 3/45 = 7%; Arm B T-DXd/anastrozole 1/29 = 3%; Arm C T-DXd->TC 5/58 = 9%. RCB0/1: 7/45 = 16%; 5/29 = 17%; 10/58 = 17%. By cycles, RCB0 / RCB1: Arm A 6 cycles (N=15) 0 / 13%; Arm A 8 cycles (N=30) 10% / 7%; Arm B 6 cycles (N=14) 0 / 7%; Arm B 8 cycles (N=15) 7% / 20%; Arm C 8 cycles (N=58) 9% / 9%. *3 pts with no surgery results enrolled to 8 cycles of treatment (1 withdrew consent; 1 expired; 1 had PD); **2 pts with no surgery results (withdrew consent/loss to follow-up). RCB 0 = pCR. Histology or IHC status did not appear to be associated with RCB response.

Philippe Aftimos, MD @aftimosp

Safety summary

ESMO 2026 · LBA23 · Oct 23, 2026

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TALENT safety summary slide: grade 3 or higher treatment-related adverse events 24%, 17% and 28%; one treatment-related death; three grade 2 ILD - TALENT, ESMO 2026 LBA23, presenter Sara A. Hurvitz, MD (photo shared by Philippe Aftimos, MD )

Slide text (transcribed by KOL Pulse from the slide images) [Image 1] TALENT: Addition of Third Arm. Stage I: any arm with >=2 pCR pass to Stage II expansion. N=58 randomized 1:1 to Arm A or Arm B. Arm A T-DXd 5.4 mg/kg: passed, enroll additional patients. Arm B T-DXd 5.4 mg/kg + anastrozole (+GnRH analog for men/premenopausal women): STOP. Arm C (N=29) T-DXd x 4 -> TC x 4: enroll additional patients*. *Arm C started enrollment after completion of Arm A/B. pCR: ypT0/is, ypN0. --- [Image 2] Pathologic Response (by arm and cycles). pCR rate: Arm A T-DXd 3/45 = 7%; Arm B T-DXd/anastrozole 1/29 = 3%; Arm C T-DXd->TC 5/58 = 9%. RCB0/1: 7/45 = 16%; 5/29 = 17%; 10/58 = 17%. By cycles, RCB0 / RCB1: Arm A 6 cycles (N=15) 0 / 13%; Arm A 8 cycles (N=30) 10% / 7%; Arm B 6 cycles (N=14) 0 / 7%; Arm B 8 cycles (N=15) 7% / 20%; Arm C 8 cycles (N=58) 9% / 9%. *3 pts with no surgery results enrolled to 8 cycles of treatment (1 withdrew consent; 1 expired; 1 had PD); **2 pts with no surgery results (withdrew consent/loss to follow-up). RCB 0 = pCR. Histology or IHC status did not appear to be associated with RCB response. --- [Image 3] Safety Summary, Arm A T-DXd (N=45) / Arm B T-DXd/anastrozole (N=29) / Arm C T-DXd->TC (N=58), n (%). TRAEs grade >=3: 11 (24) / 5 (17) / 16 (28). Treatment-related SAEs: 2 (4) / 1 (3) / 10 (17). TRAEs leading to any dose reduction: 4 (9) / 0 / 9 (16). TRAEs leading to any drug interruption: 5 (11) / 3 (10) / 5 (9). TRAEs leading to any treatment discontinuation: 2 (4) / 3 (10) / 5 (9). Any TRAEs with outcome of death: 1 (2) / 0 / 0. Adverse event of special interest, drug-related ILD/pneumonitis, grade 2 (all were grade 2): 0 / 1 (3) / 2 (3). --- [Image 4] Conclusions. Neoadjuvant T-DXd demonstrated modest clinical activity in HER2 low, HR+ localized breast cancer. Addition of endocrine therapy to T-DXd did not improve pCR rate (pCR rate T-DXd: 7%, T-DXd + anastrozole 3%). Sequencing T-DXd with multiagent chemotherapy only marginally improved pCR rate (pCR rate T-DXd: 7%, T-DXd->TC 9%). Safety: nausea and fatigue were the most common AE; 3 cases of grade 2 ILD; 1 patient death. HER2 protein levels decreased in Arms A&B after treatment with T-DXd. Higher baseline HER2 protein level may be associated with pCR in Arms A&B but sample size is small and data from Arm C are pending. Ongoing analyses include: event free survival; breast conserving surgery rates; biomarkers: ctDNA, whole genome sequencing, intrinsic subtyping, multiplex IHC, RNA seq transcriptomic analyses; patient-reported outcomes; ovarian function.

Gaia Griguolo@GaiaGriguolo

Original study design and cycle amendment

ESMO 2026 · LBA23 · Oct 23, 2026

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TALENT study design slide: Arm A T-DXd 5.4 mg/kg vs Arm B T-DXd plus anastrozole, N=58 randomized 1:1, 6 or 8 cycles then surgery - TALENT, ESMO 2026 LBA23, presenter Sara A. Hurvitz, MD (photo shared by Gaia Griguolo)

Slide text (transcribed by KOL Pulse from the slide images) [Image 1] TALENT: Study Design. Study population: hormone receptor-positive; HER2-low (by local and/or central review); stage II-III; operable; men or pre-/post-menopausal women. N=58 (1:1), stratified by HER2 expression level (1+ vs 2+) and menopausal status (pre vs post). Arm A: T-DXd 5.4 mg/kg. Arm B: T-DXd 5.4 mg/kg + anastrozole (+GnRH analog for men/premenopausal women). Treatment: 6 or 8 cycles* + EOT, then surgery**. *Originally, 6 cycles of treatment were given but after 29 patients were enrolled, an amendment increased the number of treatment cycles to 8 cycles. **After surgery, adjuvant therapy was per the discretion of the treating provider. --- [Image 2] TALENT: Addition of Third Arm. Stage I: any arm with >=2 pCR pass to Stage II expansion. N=58 randomized 1:1 to Arm A or Arm B. Arm A T-DXd 5.4 mg/kg: passed, enroll additional patients. Arm B T-DXd 5.4 mg/kg + anastrozole (+GnRH analog for men/premenopausal women): STOP. Arm C (N=29) T-DXd x 4 -> TC x 4: enroll additional patients*. *Arm C started enrollment after completion of Arm A/B. pCR: ypT0/is, ypN0. --- [Image 3] Pathologic Response (by arm and cycles). pCR rate: Arm A T-DXd 3/45 = 7%; Arm B T-DXd/anastrozole 1/29 = 3%; Arm C T-DXd->TC 5/58 = 9%. RCB0/1: 7/45 = 16%; 5/29 = 17%; 10/58 = 17%. By cycles, RCB0 / RCB1: Arm A 6 cycles (N=15) 0 / 13%; Arm A 8 cycles (N=30) 10% / 7%; Arm B 6 cycles (N=14) 0 / 7%; Arm B 8 cycles (N=15) 7% / 20%; Arm C 8 cycles (N=58) 9% / 9%. *3 pts with no surgery results enrolled to 8 cycles of treatment (1 withdrew consent; 1 expired; 1 had PD); **2 pts with no surgery results (withdrew consent/loss to follow-up). RCB 0 = pCR. Histology or IHC status did not appear to be associated with RCB response. --- [Image 4] Conclusions. Neoadjuvant T-DXd demonstrated modest clinical activity in HER2 low, HR+ localized breast cancer. Addition of endocrine therapy to T-DXd did not improve pCR rate (pCR rate T-DXd: 7%, T-DXd + anastrozole 3%). Sequencing T-DXd with multiagent chemotherapy only marginally improved pCR rate (pCR rate T-DXd: 7%, T-DXd->TC 9%). Safety: nausea and fatigue were the most common AE; 3 cases of grade 2 ILD; 1 patient death. HER2 protein levels decreased in Arms A&B after treatment with T-DXd. Higher baseline HER2 protein level may be associated with pCR in Arms A&B but sample size is small and data from Arm C are pending. Ongoing analyses include: event free survival; breast conserving surgery rates; biomarkers: ctDNA, whole genome sequencing, intrinsic subtyping, multiplex IHC, RNA seq transcriptomic analyses; patient-reported outcomes; ovarian function.

Kazuki Nozawa, MD@kazuki_nozawa

HER2 protein quantification (TROPLEX)

ESMO 2026 · LBA23 · Oct 23, 2026

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TALENT HER2 protein quantification by TROPLEX slide: median HER2 fell from 707 to 150 (Arm A) and 778 to 83 amol/mm2 (Arm B) from baseline to surgery - TALENT, ESMO 2026 LBA23, presenter Sara A. Hurvitz, MD (photo shared by Kazuki Nozawa, MD)

Slide text (transcribed by KOL Pulse from the slide images) [Image 1] TALENT: Biomarker Collection & Imaging Assessments. Arm A T-DXd 5.4 mg/kg; Arm B T-DXd 5.4 mg/kg + anastrozole; Arm C T-DXd x 4 -> TC x 4; then surgery. Tumor sample from archival or fresh biopsy at baseline, biopsy between C1D17-C1D21, and tumor sample at surgery. Circulating tumor DNA analysis collected at baseline, C1D1, C2D1 and end of treatment. Tumor imaging performed (ultrasound and mammogram) at baseline and EOT; ultrasound or mammogram at cycle 2 (modality at the discretion of the investigator). All tissue collected for study: pathology centrally reviewed. --- [Image 2] Pathologic Response (by arm and cycles). pCR rate: Arm A T-DXd 3/45 = 7%; Arm B T-DXd/anastrozole 1/29 = 3%; Arm C T-DXd->TC 5/58 = 9%. RCB0/1: 7/45 = 16%; 5/29 = 17%; 10/58 = 17%. By cycles, RCB0 / RCB1: Arm A 6 cycles (N=15) 0 / 13%; Arm A 8 cycles (N=30) 10% / 7%; Arm B 6 cycles (N=14) 0 / 7%; Arm B 8 cycles (N=15) 7% / 20%; Arm C 8 cycles (N=58) 9% / 9%. *3 pts with no surgery results enrolled to 8 cycles of treatment (1 withdrew consent; 1 expired; 1 had PD); **2 pts with no surgery results (withdrew consent/loss to follow-up). RCB 0 = pCR. Histology or IHC status did not appear to be associated with RCB response. --- [Image 3] HER2 Protein Quantification (amol/mm2) by TROPLEX. HER2 protein levels were similar for Arms A and B. HER2 levels significantly decreased over time (p<0.05) after treatment with T-DXd: Arm A 707 -> 334 -> 150; Arm B 778 -> 331 -> 83 (baseline -> cycle 2 -> surgery). Arm A: T-DXd (29/45); Arm B: T-DXd + anastrozole (21/29). Sample size with tissue: baseline (n=50), cycle 2 (n=47), surgery (n=44). Measured in the QDAP CLIA lab at Yale University Department of Pathology. --- [Image 4] Conclusions. Neoadjuvant T-DXd demonstrated modest clinical activity in HER2 low, HR+ localized breast cancer. Addition of endocrine therapy to T-DXd did not improve pCR rate (pCR rate T-DXd: 7%, T-DXd + anastrozole 3%). Sequencing T-DXd with multiagent chemotherapy only marginally improved pCR rate (pCR rate T-DXd: 7%, T-DXd->TC 9%). Safety: nausea and fatigue were the most common AE; 3 cases of grade 2 ILD; 1 patient death. HER2 protein levels decreased in Arms A&B after treatment with T-DXd. Higher baseline HER2 protein level may be associated with pCR in Arms A&B but sample size is small and data from Arm C are pending. Ongoing analyses include: event free survival; breast conserving surgery rates; biomarkers: ctDNA, whole genome sequencing, intrinsic subtyping, multiplex IHC, RNA seq transcriptomic analyses; patient-reported outcomes; ovarian function.

Sara Tolaney@stolaney1

Ki-67 by arm and timepoint

ESMO 2026 · LBA23 · Oct 23, 2026

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TALENT Ki-67 expression by arm and timepoint slide: Ki-67 fell from baseline to cycle 2 and to surgery in all arms - TALENT, ESMO 2026 LBA23, presenter Sara A. Hurvitz, MD (photo shared by Sara Tolaney)

Slide text (transcribed by KOL Pulse from the slide images) [Image 1] Pathologic Response (by arm and cycles). pCR rate: Arm A T-DXd 3/45 = 7%; Arm B T-DXd/anastrozole 1/29 = 3%; Arm C T-DXd->TC 5/58 = 9%. RCB0/1: 7/45 = 16%; 5/29 = 17%; 10/58 = 17%. By cycles, RCB0 / RCB1: Arm A 6 cycles (N=15) 0 / 13%; Arm A 8 cycles (N=30) 10% / 7%; Arm B 6 cycles (N=14) 0 / 7%; Arm B 8 cycles (N=15) 7% / 20%; Arm C 8 cycles (N=58) 9% / 9%. *3 pts with no surgery results enrolled to 8 cycles of treatment (1 withdrew consent; 1 expired; 1 had PD); **2 pts with no surgery results (withdrew consent/loss to follow-up). RCB 0 = pCR. Histology or IHC status did not appear to be associated with RCB response. --- [Image 2] Objective Response Rate (intention-to-treat). Arm A (T-DXd), N=45: ORR 28/45 = 62%; CR 5/45 = 11%; PR 23/45 = 51%. Arm B (T-DXd + anastrozole), N=29: ORR 19/29 = 66%; CR 2/29 = 7%; PR 17/29 = 59%. Arm C (T-DXd x4 -> TC x4), N=58: ORR 42/58 = 72%; CR 9/58 = 16%; PR 33/58 = 57%. 3 patients did not have EOT imaging, but were included in the ITT denominator for ORR analysis per protocol. Waterfall plot: change in tumor size after treatment vs baseline per RECIST v1.1. --- [Image 3] HER2 Protein Quantification (amol/mm2) by TROPLEX. HER2 protein levels were similar for Arms A and B. HER2 levels significantly decreased over time (p<0.05) after treatment with T-DXd: Arm A 707 -> 334 -> 150; Arm B 778 -> 331 -> 83 (baseline -> cycle 2 -> surgery). Arm A: T-DXd (29/45); Arm B: T-DXd + anastrozole (21/29). Sample size with tissue: baseline (n=50), cycle 2 (n=47), surgery (n=44). Measured in the QDAP CLIA lab at Yale University Department of Pathology. --- [Image 4] Expression of Ki-67 (IHC) by arm and timepoint. Ki-67 decreased from baseline to cycle 2 in all arms: Arm A p=0.015; Arm B p<0.001; Arm C p<0.004. Ki67 decreased from baseline to surgery in all arms: Arm A, B, C p<0.001. Samples available: Arm A baseline 45/45, cycle 2 41/45, surgery 36/45; Arm B baseline 29/29, cycle 2 27/29, surgery 28/29; Arm C baseline 58/58, cycle 2 56/58, surgery 46/58. Central laboratory: Breast Cancer Analysis Laboratory, USC/Norris Comprehensive Cancer Center.

Yakup Ergün@dr_yakupergun

LBA23 abstract (ESMO 2026 programme)

ESMO 2026 · LBA23 · Oct 23, 2026

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TALENT ESMO 2026 LBA23 abstract (Hurvitz et al.) with RCB, ORR and safety table by arm (photo shared by Yakup Ergün)

Abstract text (verbatim from the ESMO 2026 programme) Title: LBA23 - 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 Background Pathologic complete response (pCR) in HR+/HER2-negative breast cancer (BC) is uncommon. T-DXd, a HER2-targeted antibody drug conjugate, improves progression-free and overall survival vs chemotherapy in metastatic HER2-low BC. TALENT (NCT04553770) is a phase II, 2-stage neoadjuvant study evaluating T-DXd + endocrine therapy or in sequence with chemotherapy in pts with HR+/HER2-low early BC. Methods Pts with untreated, operable invasive early HR+/HER2-low BC were randomized 1:1 to receive 6 cy of T-DXd (5.4 mg/kg q21d) alone (Arm A) or with anastrozole (1 mg PO QD) (Arm B). An arm was expanded if ≥2 pCR (RCB0) were observed. After 29 pts enrolled, subsequent pts received 8 cy. After Arms A/B, Arm C was added to evaluate 4 cy T-DXd → 4 cy docetaxel 75 mg/m2 + cyclophosphamide 600 mg/m2 (TC) in <58 pts. Biopsies were taken at baseline, pre-cy2 & surgery. Imaging/biomarkers were assessed at baseline, cy 2 & surgery. Endpoints: Residual Cancer Burden (RCB), safety, overall response rate (ORR) & biomarkers. Ki67, HER2, ER & PR were evaluated centrally, and TROP2 & HER2 levels were quantified (quant) by TROPLEX for Arms A & B. Results From 11/2020 - 02/2026, 132 pts were enrolled. Pts in Arm C were more likely to have node+ disease (81%) vs. Arms A/B (53%, 55%). Overall rates of pCR/near-pCR (RCB 0/1) were 16% (Arm A), 17% (Arm B), and 17% (10/58 Arm C). HER2 levels were higher in pts with RCB0 (2691 & 1221 amol/mm2) vs RCB1/2/3 (715-947 & 440-608 amol/mm2) at Baseline & cy 2, respectively. Table: LBA23 Arm A (N=45) n (%) Arm B (N=29) n (%) Arm C (N=58) n (%) Baseline characteristics Stage I/II/III 0/32 (71)/13 (29) 0/26 (90)/3 (10) 2 (3)/43 (74)/13 (22) Node+ 24 (53) 16 (55) 47 (81) Grade III 19 (42) 11 (38) 29 (50) Ki67>20% (central) 33 (73) 24 (83) 43 (74) Antigen quant (med amol/mm2) Baseline→Cy2→Surgery HER2 707→334→150 778→331→83 - TROP2 1097→1371→1001 1001→952→925 - Results: Evaluable RCB0 3/42 (7) 1/29 (3) 5/55 (9) ORR 28/42 (67) 19/29 (66) 37/57 (65) Results ITT 6 cycles (N=15) 8 cycles (N=30) 6 cycles (N=14) 8 cycles (N=15) 8 cycles (N=58) RCB0 0 3 (10) 0 1 (7) 5 (9) RCB1 2 (13) 2 (7) 1 (7) 3 (20) 5 (9) Gr >3 Treatment Emergent AE 3 (20) 8 (27) 3 (21) 2 (13) 16 (28) Interstitial Lung Disease (all Gr 2) 0 0 1 (7) 0 2 (3) Conclusions In this first study to report outcomes with neoadjuvant T-DXd in HR+/HER2-low BC, T-DXd–based therapy was associated with low pCR rates. ILD was rare. HER2 was higher in tumors with RCB0 versus RCB1/2/3, suggesting HER2 level may correlate with treatment outcome. HER2 levels declined significantly on treatment, whereas TROP2 expression remained stable. ER, PR, & Ki67 analyses will be presented.

KOL-Made Infographics

Summary graphics designed by physicians (not conference slides). Values are as the authors drew them; the ORR figures (65–67%) are the abstract’s evaluable-patient numbers. Click to enlarge.

MV Onco infographic on TALENT: the tumour shrank but the cancer survived (made by MV Chandrakanth)

@ChandrakanthMv

MV Onco infographic on TALENT part 1: ORR, pCR and pCR plus near-pCR by arm (made by MV Chandrakanth)

@ChandrakanthMv

MV Onco infographic on TALENT part 2: HER2 decline and stable TROP2 (made by MV Chandrakanth)

@ChandrakanthMv

Infographic on TALENT LBA23: tumors shrank, pCR stayed low, by arm (made by Dr Rishabh Jain)

@DrRishabhOnco

Summary table of TALENT LBA23 outcomes by arm (made by Dr Amol Akhade)

@SuyogCancer

Pre-congress preview graphic on TALENT LBA23 (posted before the presentation) (made by Mustafa Özdoğan, MD)

@ozdogan_md

Community Discussion

TALENT Top Tweets

Full, verbatim posts from 21 physicians (26 posts), sorted by views and linked to the originals. Where a post’s figure differs from the presentation slide, a source note sits under it.

Yakup Ergün@dr_yakupergun

#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.

3.7K views 42 likes18 RT 2026-10-23

Dr Amol Akhade@SuyogCancer

Probably first negative trial for Trastuzumab deruxtecan. Talent trial. For early stage HR positive Her2 low EBC @myESMO #esmo26 @OncoAlert https://t.co/1m62ih9PrE

2.4K views 29 likes8 RT 2026-10-23

Paolo Tarantino@PTarantinoMD

TALENT: neoadjuvant T-DXd, +/- anastrozole or TC, led to a disappointing pCR rate of <10% across arms for HR+ eBC. A hint of superior benefit was observed in patients with high HS-HER2 at baseline. Biomarkers clearly needed to unlock the potential of ADCs in the curative setting. https://t.co/gwUJ6UxMUT

1.2K views 21 likes9 RT 2026-10-23

Sara Tolaney@stolaney1

TALENT trial presented by Sara Hurvitz: Preop TDXd in HR+ HER2-low breast cancer Preop TDXd: 7% TDXd+AI: 3% TDXd-->TC: 9% Adding endocrine therapy and sequencing chemo with TDXd didn't seem to improve pCR @OncoAlert #ESMO2026 https://t.co/dArlOO4Mpa

914 views 20 likes16 RT 2026-10-23

Yakup Ergün@dr_yakupergun

In TALENT, adding anastrozole did not increase pCR. In light of these data, how should we approach concurrent ET with T-DXd in DB-05/09? Are subgroup results by ET use available? What are your thoughts? #ESMO26 https://t.co/KjcRXZkCBd

853 views 7 likes0 RT 2026-10-23

Erika Hamilton, MD, FASCO@ErikaHamilton9

TALENT- neoadj T-DXd in HR+/HER2-low #bcsm RCB0/1: 🔹 T-DXd alone: 16% 🔹 T-DXd + anastrozole: 17% 🔹 T-DXd → TC chemo: 17% *no pCRs w/out 8 cycles Despite high ORR ~66%, pCR LOW! We know w/ HR+ we don't get high pCRs rates, but still disappointing #ESMO26 #ESMOAmbassadors https://t.co/smlF5DmAAt

844 views 10 likes8 RT 2026-10-23

Dr Amol Akhade@SuyogCancer

🚨 ESMO 2026 | TALENT Trial (LBA23) Disappointing results for neoadjuvant T-DXd in HR+/HER2-low early breast cancer ? 🔹 T-DXd alone: pCR/near-pCR 16% 🔹 T-DXd + anastrozole: 17% 🔹 T-DXd → TC chemotherapy: 17% Despite ORR ~65–67%, pCR rates remained low. Adding endocrine therapy or sequential chemotherapy did not meaningfully improve response. Looking forward towards full dataset. @OncoAlert @myESMO @OncBrothers #ESMO26

Posted before the presentation, from the LBA23 abstract. The abstract reports ORR in evaluable patients (67%, 66%, 65%); the presentation slide reports ORR in all treated patients (62%, 66%, 72%).

820 views 2 likes1 RT 2026-10-22

Mitsuo Terada, MD, PhD@乳腺科医@MamMa_mimumemo

TALENT試験。HR+/HER2-low早期乳がんに術前T-DXd±アナストロゾール、T-DXd→TCを検討。ORR約65%だがRCB0は3〜9%。ILDは稀。 HER2高発現例でRCB0が多く、治療中HER2は低下。 #ESMO26 https://t.co/VV2CvR6ARN

547 views 7 likes1 RT 2026-10-23

Dr Rishabh Jain@DrRishabhOnco

🚨 TALENT | #ESMO26 | LBA23 T-DXd in HR+/HER2-low early breast cancer: Tumors shrink, but pCR remains low! 📊 pCR rates: • T-DXd alone: 7% • + Anastrozole: 3% • → Chemotherapy: 9% ✅ ORR: 65–67% across arms 🔍 Verdict: Encouraging tumor shrinkage, but limited pathologic clearance. No clear benefit from adding endocrine therapy or sequential chemotherapy. Not practice-changing. @ESMO_open @my_esmo @oncoalert #ESMO26 #BreastCancer

539 views 3 likes1 RT 2026-10-23

Stephanie Graff, MD, FACP, FASCO@DrSGraff

TALENT—neoadj TDXd (6-8 cycles) +/- AI in HER2 low HR+ early stage breast ca ypCR // RCB TDXd 7% // 16% T-DXd/AI: 3% // 9% T-DXd→ TC: 17% // 17% Author concludes “modest” benefit; I would say “disappointing”. ypCR just isn’t the same endpoint w/ ER+ disease #ESMO26 @OncoAlert https://t.co/3jg6NTqiyH

Source note: the presentation slide reports pCR (RCB0) 9% (5/58) and RCB0/1 17% (10/58) for T-DXd followed by TC.

517 views 16 likes7 RT 2026-10-23

Niklas Klümper@niklas_kluemper

🚨 Important biomarker signal from #ESMO2026—highly relevant beyond breast cancer! In the neoadjuvant TALENT trial T-DXd achieved relatively low pCR/near-pCR rates (16–17%) in HER2-low breast cancer. Importantly, higher baseline HER2 expression was associated with better pathological response, while HER2 expression declined substantially during treatment. Could the same principle apply to perioperative enfortumab vedotin + pembrolizumab in MIBC? We urgently need to understand whether low or absent membranous NECTIN4 expression identifies patients less likely to achieve pCR—and potentially at higher risk of recurrence despite EV+pembro. Histology, quantitative membranous NECTIN4 expression, spatial heterogeneity and ctDNA dynamics should be integrated into prospective biomarker studies. @Markuseckstein3 @DrRosenbergMSK @Dr_Aggen Precision perioperative therapy must start before cycle 1—not only after cystectomy. 🔬 @OncoAlert Faculty @DrChoueiri , @tompowles1 , @apolo_andrea , @neerajaiims , @montypal , @Silke_Gillessen , @AOmlin , @brian_rini , @PGrivasMDPhD , @TiansterZhang , @amerseburger , @DrDanielHeng , @HHammersMD , @scocmem , @AndreaNecchi , @AmandaNizamMD , @drenriquegrande , @nataliagandur , @AlbigesL , @cdanicas , @declangmurphy , @seanmmcbride , @shilpaonc , @DrRanaMcKay , @scserendipity1 , @DrYukselUrun , @ravikanesvaran , @BraunMDPhD , @EfstathiouEleni , @mzugman , @crisbergerot

514 views 12 likes8 RT 2026-10-23

Yakup Ergün@dr_yakupergun

#ESMO26 | TALENT In HR+/HER2-low early breast cancer, neoadjuvant T-DXd ± anastrozole or sequential chemotherapy achieved pCR/near-pCR rates of only 16–17%. Adding anastrozole or sequential chemotherapy showed no clear benefit. https://t.co/pWaagTkKtu https://t.co/KjcRXZkCBd

507 views 4 likes1 RT 2026-10-23

Matteo Lambertini, MD PhD@matteolambe

Oral abstract #BreastCancer session at #ESMO26: updated data from the TALENT trial showing activity of neoadjuvant #TrastuzumabDeruxtecan in HER2-low HR+ disease @OncoAlert @myESMO https://t.co/Lk2cvsDAFg

505 views 18 likes10 RT 2026-10-23

Kazuki Nozawa, MD@kazuki_nozawa

TALENT trial #ESMO26 Neoadjuvant T-DXd showed modest efficacy (pCR 3–9%), with limited benefit from additional therapy and potential safety concerns. https://t.co/XCmqAJXtYW

501 views 6 likes3 RT 2026-10-23

Philippe Aftimos, MD @aftimosp

Some take-away points from @BarbaraPistill2 ‘s dicussion of the anti-HER2 ADCs abstracts 🔹Trials with 3 ADCs with the same target, linker & payload class 🔹In TALENT, the low pCR rate is comparable to NACT and other ADCs in HR+/ HER2- EBC @myESMO #ESMOAmbassadors #ESMO26 1/2 https://t.co/xITGw7JxRA

409 views 8 likes5 RT 2026-10-23

Mustafa Özdoğan, MD@ozdogan_md

Can an ADC move from metastatic benefit into curative-intent early breast cancer? At #ESMO26, TALENT (LBA23) will test neoadjuvant trastuzumab deruxtecan in HER2-low / HR+ early breast cancer-with or without anastrozole, or sequenced with chemotherapy. The real question: activity is not enough. How should we weigh efficacy, ILD risk, and treatment positioning in early disease? Presenter: Sara Hurvitz #bcsm

Posted before the presentation (preview).

383 views 13 likes8 RT 2026-10-22

MV Chandrakanth@ChandrakanthMv

TALENT | ESMO 2026 | LBA23 The tumour shrank. But the cancer survived. Neoadjuvant T-DXd in HR+/HER2-low breast cancer: • ORR: 65–67% • pCR: Only 3–9% • Adding anastrozole or sequential TC showed no clear pCR improvement. The biological surprise: HER2 expression declined during treatment, while TROP2 remained relatively stable. TAKE-HOME: Shrinkage ≠ eradication. Low pCR does not necessarily exclude long-term benefit. Residual disease biology may hold important clues to ADC resistance. Ref: Hurvitz SA et al. TALENT final results. ESMO 2026; LBA23. NCT04553770. #MVOnco #ESMO2026 #BreastCancer #TDXd

318 views 4 likes0 RT 2026-10-23

Philippe Aftimos, MD @aftimosp

T-DXd as neoadjuvant therapy for HR+/ HER2-low early breast cancer: 🔹pCR rate of 7%. 8 cycles needed. 🔹No benefit from the addition of endocrine therapy in combination. 🔸1 fatal adverse event. Low rate of ILD. 🔸More grade 3 AEs in the arm with chemo #ESMOAmbassadors #ESMO26 https://t.co/dkFjN8HNqy

308 views 3 likes4 RT 2026-10-23

Armando Orlandi@ArmandOrlandi

Cowabunga! 🌊 Riding the Breast Cancer Wave 🏄🏻‍♂️🤙🏻 from #ESMO26 TALENT: neoadjuvant trastuzumab deruxtecan in luminal HER2-low tumors.  Residual Cancer Burden 0/1: 16–17%. Tumors shrink, rarely disappear. Wrong endpoint or wrong combination? @OncoAlert @Larvol https://t.co/U9z38ZdilM

285 views 4 likes5 RT 2026-10-23

Gaia Griguolo@GaiaGriguolo

TALENT trial at #ESMO26 Neoadjuvant T-DXd +/- anastrozole or sequentially with TCx4 shows modest activity in HER2-low Hr+ early BC pCR TDXd 7%, TDXd +anastroxole 3%, TDXd x 4 -> TC×4 9% High baseline levels of HER2 prot potentially associated with higher pCR rates @OncoAlert https://t.co/8P5pLJfrg6

266 views 7 likes7 RT 2026-10-23

Carmen Criscitiello@CarmenCriscit

TALENT: neoadjuvant Tdxd in HER2-low, HR+ early breast cancer - modest activity, pCR ~7%, not improved by adding anastrozole or sequencing chemotherapy. A useful reminder that HER2-low is not the same as HER2-driven in the curative setting. #ESMO26 #ESMOAmbassadors @myESMO https://t.co/ajzGVU6sAE

184 views 7 likes2 RT 2026-10-23

Oncology Brothers@OncBrothers

3. TALENT: Neoadj TDXd ± AI or → TC in HR+/HER2-low early BC. - pCR: T-DXd 7%; +AI 3%; →TC 9% - Adding ET or seq chemo did not meaningfully improve pCR. Not practice-changing. What does this mean for triple positive mBC? 👇👇 4/8 https://t.co/pjM1GHYOOb https://t.co/VQxclEhYKm

156 views 1 likes0 RT 2026-10-23

Evandro de Azambuja, MD, PhD@E_de_Azambuja

Low activity of TDXD in HER2 low ER+ EBC #ESMO26 #ESMOAmbassadors #ESMOcommunity @myESMO https://t.co/OSRlebNcRP

151 views 3 likes0 RT 2026-10-23

Kristina Jankovic, MD@JankovicK

#TALENT at #ESMO26 🇪🇸 : neoadjuvant T-DXd alone, T-DXd + anastrozole, or T-DXd followed by TC showed high response rates but pCR <10% across all arms in HR+/HER2-low early #BreastCancer Better biomarkers are needed to guide patient selection. @OncoAlert https://t.co/fLXRulAGXD

142 views 2 likes2 RT 2026-10-23

Philippe Aftimos, MD @aftimosp

T-DXd is approved in HER2-low & ultra-low HR+/HER2- MBC after it improved outcomes in pivotal ph3 trials. ❓A role for T-DXd in HER2-low/HR+ early breast cancer? Final resuls from TALENT presented today at #ESMO26 are described & commented by @breastDoktor #ESMOAmbassadors 👇 https://t.co/hzd7KBcJk8

132 views 2 likes0 RT 2026-10-23

Aydah AlAwadhi, MD 🇦🇪@Aydah_AlAwadhi

ESMO 2026 | TALENT Trial Neoadjuvant T-DXd: modest activity in HR+/HER2-low early breast cancer. pCR rates: T-DXd: 7% T-DXd + anastrozole: 3% T-DXd → chemotherapy: 9% Adding endocrine therapy did not improve pCR, while sequential chemotherapy offered only marginal benefit. ⚠️ 3 cases of grade 2 ILD and 1 patient death. Take-home: Impressive metastatic efficacy has not translated into meaningful neoadjuvant activity. Not practice-changing. #ESMO2026 #BreastCancer #ESMO26 @OncoAlert

74 views 0 likes0 RT 2026-10-23

Trial Background

About the TALENT Trial

TALENT asked whether trastuzumab deruxtecan, which improves progression-free and overall survival over chemotherapy in metastatic HER2-low breast cancer, could produce pathologic complete responses before surgery in HR-positive, HER2-low early breast cancer, a setting where pCR is uncommon. The investigator-initiated trial (TRIO-US B-12) is sponsored by UCLA’s Jonsson Comprehensive Cancer Center with Translational Research in Oncology (TRIO-US) and funded by Daiichi Sankyo. Arms A and B were randomized 1:1; Arm B (with anastrozole) stopped after stage 1, while Arm A and the later-added Arm C (T-DXd followed by docetaxel plus cyclophosphamide) were expanded. Interim stage-1 results were first reported at SABCS 2022 (abstract GS2-03); the ESMO 2026 LBA23 presentation by Sara A. Hurvitz, MD, reports the final results. Event-free survival, breast-conserving surgery rates and further biomarker analyses are ongoing.

ESMO 2026 programme (LBA23) ClinicalTrials.gov DESTINY-Breast06 profile

#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.
— Yakup Ergün (@dr_yakupergun) Oct 23, 2026

Study Design

Trial Methodology & Results

Study Design

Phase 2, open-label, two-stage neoadjuvant study (NCT04553770). Arms A/B randomized 1:1 (N=58 in stage 1), stratified by HER2 IHC 1+ vs 2+ and menopausal status; an arm advanced if ≥2 pCRs were seen. 132 patients enrolled, Nov 2020 to Feb 2026.

Population

Previously untreated, operable stage II–III HR-positive, HER2-low (IHC 1+ or 2+/ISH-) breast cancer; men and pre- or postmenopausal women. Node-positive: 53%, 55% and 81% (Arms A, B, C).

Interventions

Arm A: T-DXd 5.4 mg/kg every 3 weeks. Arm B: T-DXd plus anastrozole 1 mg daily (+GnRH analog for men/premenopausal women). 6 cycles, then 8 after 29 patients. Arm C: 4 cycles T-DXd, then 4 cycles docetaxel 75 mg/m² plus cyclophosphamide 600 mg/m².

Endpoints

Residual cancer burden (RCB; RCB0 = pCR, ypT0/is ypN0), safety, ORR and biomarkers (central Ki67, HER2, ER, PR; HER2 and TROP2 quantified by TROPLEX in Arms A/B).

Presenter

Sara A. Hurvitz, MD (Fred Hutch Cancer Center, University of Washington); senior author Aditya Bardia, MD.

Data Cut

Final results; no data-cutoff date is printed on the abstract or slides. Enrollment Nov 2020 to Feb 2026.

Pathologic response (RCB)

pCR (RCB0) was 7% (3/45), 3% (1/29) and 9% (5/58), and pCR or near-pCR (RCB0/1) 16%, 17% and 17% (LBA23 presentation slides). The abstract gives the same pCR rates in evaluable patients (3/42, 1/29, 5/55). In Arms A and B, no pCRs occurred with 6 cycles; with 8 cycles RCB0 was 10% (Arm A, N=30) and 7% (Arm B, N=15). Five patients had no surgery result (3 in Arm A: 1 withdrew consent, 1 died, 1 progressed; 2 in Arm C).

pCR 7% · 3% · 9%
ESMO 2026 LBA23 (programme) · ClinicalTrials.gov NCT04553770

TALENT—neoadj TDXd (6-8 cycles) +/- AI in HER2 low HR+ early stage breast ca ypCR // RCB TDXd 7% // 16% T-DXd/AI: 3% // 9% T-DXd→ TC: 17% // 17% Author concludes “modest” benefit; I would say “disappointing”. ypCR just isn’t the same endpoint w/ ER+ disease #ESMO26 @OncoAlert https://t.co/3jg6NTqiyH
— Stephanie Graff, MD, FACP, FASCO (@DrSGraff) Oct 23, 2026

Source note: the presentation slide reports pCR (RCB0) 9% (5/58) and RCB0/1 17% (10/58) for T-DXd followed by TC.

Objective response

The abstract and the presentation use different denominators. The slide counts all patients who received at least one cycle; the abstract counts evaluable patients. The two also differ for Arm C (42/58 vs 37/57). Both are shown as published.

Objective response	Arm A: T-DXd	Arm B: T-DXd + anastrozole	Arm C: T-DXd → TC
All treated patients (presentation slide)	28/45 (62%)	19/29 (66%)	42/58 (72%)
Complete / partial response (slide)	11% / 51%	7% / 59%	16% / 57%
Evaluable patients (abstract)	28/42 (67%)	19/29 (66%)	37/57 (65%)

ESMO 2026 LBA23 (programme)

Safety

Nausea and fatigue were the most common adverse events. The abstract reports grade ≥3 treatment-emergent adverse events of 20% and 27% (Arm A, 6 and 8 cycles), 21% and 13% (Arm B) and 28% (Arm C) (LBA23 abstract); the slide reports treatment-related events by arm (LBA23 presentation slides):

Treatment-related AEs, n (%)	Arm A (N=45)	Arm B (N=29)	Arm C (N=58)
Grade ≥3	11 (24)	5 (17)	16 (28)
Serious	2 (4)	1 (3)	10 (17)
Leading to dose reduction	4 (9)	0	9 (16)
Leading to discontinuation	2 (4)	3 (10)	5 (9)
Outcome of death	1 (2)	0	0
Drug-related ILD/pneumonitis (all grade 2)	0	1 (3)	2 (3)

3 grade 2 ILD · 1 treatment-related death
ClinicalTrials.gov NCT04553770

T-DXd as neoadjuvant therapy for HR+/ HER2-low early breast cancer: 🔹pCR rate of 7%. 8 cycles needed. 🔹No benefit from the addition of endocrine therapy in combination. 🔸1 fatal adverse event. Low rate of ILD. 🔸More grade 3 AEs in the arm with chemo #ESMOAmbassadors #ESMO26 https://t.co/dkFjN8HNqy
— Philippe Aftimos, MD  (@aftimosp) Oct 23, 2026

Biomarkers

Median HER2 protein (TROPLEX, amol/mm²) fell from 707 to 334 to 150 in Arm A and from 778 to 331 to 83 in Arm B (baseline, cycle 2, surgery), while TROP2 stayed relatively stable (1097 to 1371 to 1001; 1001 to 952 to 925). HER2 was higher in tumors that reached RCB0 (2691 and 1221 amol/mm² at baseline and cycle 2) than with residual disease (715–947 and 440–608) (LBA23 abstract). Ki-67 fell from baseline to surgery in all arms (p<0.001) (LBA23 presentation slides).

ESMO 2026 LBA23 (programme)

TALENT: neoadjuvant T-DXd, +/- anastrozole or TC, led to a disappointing pCR rate of <10% across arms for HR+ eBC. A hint of superior benefit was observed in patients with high HS-HER2 at baseline. Biomarkers clearly needed to unlock the potential of ADCs in the curative setting. https://t.co/gwUJ6UxMUT
— Paolo Tarantino (@PTarantinoMD) Oct 23, 2026

Sources: ESMO 2026 abstract LBA23 and presentation (Sara A. Hurvitz, MD, October 23, 2026); ClinicalTrials.gov NCT04553770; FDA. Slides were shared on X by the physicians credited in Key Slides.

Major Media & Publications

TALENT in the News

Abstract

LBA23: 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

ESMO 2026Oct 23, 2026

Press

Neoadjuvant trastuzumab deruxtecan shows clinical activity in patients with HER2-low breast cancer (SABCS 2022 interim results)

AACRDec 7, 2022

Media

Neoadjuvant T-DXd demonstrates activity in phase II study of patients with HER2-low breast cancer

The ASCO PostJan 25, 2023

FDA

FDA approves fam-trastuzumab deruxtecan-nxki for unresectable or metastatic HR-positive, HER2-low or HER2-ultralow breast cancer

FDAJan 27, 2025

Registry

Trastuzumab deruxtecan alone or with anastrozole for early stage HER2-low, HR-positive breast cancer (NCT04553770)

ClinicalTrials.govRecord

FAQ

TALENT Questions

What is the TALENT trial?

TALENT (TRIO-US B-12; NCT04553770) is a phase 2, two-stage neoadjuvant trial in operable, previously untreated HR-positive, HER2-low (IHC 1+ or 2+, ISH non-amplified) stage II-III breast cancer. Patients were randomized 1:1 to trastuzumab deruxtecan 5.4 mg/kg every 3 weeks alone (Arm A) or with anastrozole (Arm B), for 6 cycles and, after an amendment once 29 patients were enrolled, 8 cycles. A third arm (Arm C) then gave 4 cycles of T-DXd followed by 4 cycles of docetaxel plus cyclophosphamide (TC). 132 patients were enrolled from November 2020 to February 2026. The lead sponsor is UCLA's Jonsson Comprehensive Cancer Center with Translational Research in Oncology (TRIO-US); funding came from Daiichi Sankyo.

What did TALENT show at ESMO 2026?

Pathologic complete response (RCB0) rates were low: 7% (3/45) with T-DXd alone, 3% (1/29) with T-DXd plus anastrozole and 9% (5/58) with T-DXd followed by TC. pCR or near-pCR (RCB0/1) was 16%, 17% and 17%. Tumors still shrank: on the presentation slides ORR was 62%, 66% and 72% in all treated patients; the abstract reports 67%, 66% and 65% in evaluable patients. The investigators concluded that neoadjuvant T-DXd showed modest activity, that anastrozole did not improve pCR and that sequencing with chemotherapy only marginally improved it.

Was TALENT a negative trial?

TALENT is a phase 2 two-stage study; an arm advanced to stage 2 if at least 2 pCRs were seen. The investigators' own conclusion was "modest clinical activity". Several physicians described the result as disappointing or not practice-changing, while others noted that pCR is a limited surrogate in HR-positive disease and that event-free survival is still being analyzed.

Is trastuzumab deruxtecan approved for early-stage HER2-low breast cancer?

No. In HER2-low breast cancer, Enhertu (fam-trastuzumab deruxtecan-nxki) is FDA approved only for unresectable or metastatic disease: after prior chemotherapy (DESTINY-Breast04, August 2022) and, for HR-positive HER2-low or HER2-ultralow disease, after one or more endocrine therapies in the metastatic setting (DESTINY-Breast06, January 2025). Neoadjuvant use as in TALENT is investigational.

What safety signals were reported in TALENT?

On the presentation slides, grade 3 or higher treatment-related adverse events occurred in 24% (Arm A), 17% (Arm B) and 28% (Arm C). There were three cases of grade 2 drug-related ILD/pneumonitis (one in Arm B, two in Arm C) and one treatment-related death (Arm A). Nausea and fatigue were the most common adverse events.

What did the biomarker analyses show?

Median HER2 protein measured by TROPLEX fell during T-DXd treatment, from 707 to 150 amol/mm2 in Arm A and from 778 to 83 amol/mm2 in Arm B (baseline to surgery), while TROP2 stayed relatively stable. Per the abstract, HER2 levels were higher in tumors that reached RCB0 than in those with residual disease, suggesting HER2 level may correlate with response; the investigators note the sample size is small.

Physician Opinions

Key KOL Sentiments - TALENT

Physician	Date	Sentiment	Post (verbatim)
Matteo Lambertini, MD PhD @matteolambe	Oct 23, 2026	● POSITIVE	Oral abstract #BreastCancer session at #ESMO26: updated data from the TALENT trial showing activity of neoadjuvant #TrastuzumabDeruxtecan in HER2-low HR+ disease @OncoAlert @myESMO https://t.co/Lk2cvsDAFg
Sara Tolaney @stolaney1	Oct 23, 2026	● NEUTRAL	TALENT trial presented by Sara Hurvitz: Preop TDXd in HR+ HER2-low breast cancer Preop TDXd: 7% TDXd+AI: 3% TDXd-->TC: 9% Adding endocrine therapy and sequencing chemo with TDXd didn't seem to improve pCR @OncoAlert #ESMO2026 https://t.co/dArlOO4Mpa
Yakup Ergün @dr_yakupergun	Oct 23, 2026	● NEUTRAL	In TALENT, adding anastrozole did not increase pCR. In light of these data, how should we approach concurrent ET with T-DXd in DB-05/09? Are subgroup results by ET use available? What are your thoughts? #ESMO26 https://t.co/KjcRXZkCBd
Mitsuo Terada, MD, PhD@乳腺科医 @MamMa_mimumemo	Oct 23, 2026	● NEUTRAL	TALENT試験。HR+/HER2-low早期乳がんに術前T-DXd±アナストロゾール、T-DXd→TCを検討。ORR約65%だがRCB0は3〜9%。ILDは稀。 HER2高発現例でRCB0が多く、治療中HER2は低下。 #ESMO26 https://t.co/VV2CvR6ARN
Niklas Klümper @niklas_kluemper	Oct 23, 2026	● NEUTRAL	🚨 Important biomarker signal from #ESMO2026—highly relevant beyond breast cancer! In the neoadjuvant TALENT trial T-DXd achieved relatively low pCR/near-pCR rates (16–17%) in HER2-low breast cancer. Importantly, higher baseline HER2 expression was associated with better pathological response, while HER2 expression declined substantially during treatment. Could the same principle apply to perioperative enfortumab vedotin + pembrolizumab in MIBC? We urgently need to understand whether low or absent membranous NECTIN4 expression identifies patients less likely to achieve pCR—and potentially at higher risk of recurrence despite EV+pembro. Histology, quantitative membranous NECTIN4 expression, spatial heterogeneity and ctDNA dynamics should be integrated into prospective biomarker studies. @Markuseckstein3 @DrRosenbergMSK @Dr_Aggen Precision perioperative therapy must start before cycle 1—not only after cystectomy. 🔬 @OncoAlert Faculty @DrChoueiri , @tompowles1 , @apolo_andrea , @neerajaiims , @montypal , @Silke_Gillessen , @AOmlin , @brian_rini , @PGrivasMDPhD , @TiansterZhang , @amerseburger , @DrDanielHeng , @HHammersMD , @scocmem , @AndreaNecchi , @AmandaNizamMD , @drenriquegrande , @nataliagandur , @AlbigesL , @cdanicas , @declangmurphy , @seanmmcbride , @shilpaonc , @DrRanaMcKay , @scserendipity1 , @DrYukselUrun , @ravikanesvaran , @BraunMDPhD , @EfstathiouEleni , @mzugman , @crisbergerot
Philippe Aftimos, MD  @aftimosp	Oct 23, 2026	● NEUTRAL	Some take-away points from @BarbaraPistill2 ‘s dicussion of the anti-HER2 ADCs abstracts 🔹Trials with 3 ADCs with the same target, linker & payload class 🔹In TALENT, the low pCR rate is comparable to NACT and other ADCs in HR+/ HER2- EBC @myESMO #ESMOAmbassadors #ESMO26 1/2 https://t.co/xITGw7JxRA
Mustafa Özdoğan, MD @ozdogan_md	Oct 22, 2026	● NEUTRAL	Can an ADC move from metastatic benefit into curative-intent early breast cancer? At #ESMO26, TALENT (LBA23) will test neoadjuvant trastuzumab deruxtecan in HER2-low / HR+ early breast cancer-with or without anastrozole, or sequenced with chemotherapy. The real question: activity is not enough. How should we weigh efficacy, ILD risk, and treatment positioning in early disease? Presenter: Sara Hurvitz #bcsm
MV Chandrakanth @ChandrakanthMv	Oct 23, 2026	● NEUTRAL	TALENT \| ESMO 2026 \| LBA23 The tumour shrank. But the cancer survived. Neoadjuvant T-DXd in HR+/HER2-low breast cancer: • ORR: 65–67% • pCR: Only 3–9% • Adding anastrozole or sequential TC showed no clear pCR improvement. The biological surprise: HER2 expression declined during treatment, while TROP2 remained relatively stable. TAKE-HOME: Shrinkage ≠ eradication. Low pCR does not necessarily exclude long-term benefit. Residual disease biology may hold important clues to ADC resistance. Ref: Hurvitz SA et al. TALENT final results. ESMO 2026; LBA23. NCT04553770. #MVOnco #ESMO2026 #BreastCancer #TDXd
Philippe Aftimos, MD  @aftimosp	Oct 23, 2026	● NEUTRAL	T-DXd as neoadjuvant therapy for HR+/ HER2-low early breast cancer: 🔹pCR rate of 7%. 8 cycles needed. 🔹No benefit from the addition of endocrine therapy in combination. 🔸1 fatal adverse event. Low rate of ILD. 🔸More grade 3 AEs in the arm with chemo #ESMOAmbassadors #ESMO26 https://t.co/dkFjN8HNqy
Armando Orlandi @ArmandOrlandi	Oct 23, 2026	● NEUTRAL	Cowabunga! 🌊 Riding the Breast Cancer Wave 🏄🏻‍♂️🤙🏻 from #ESMO26 TALENT: neoadjuvant trastuzumab deruxtecan in luminal HER2-low tumors.  Residual Cancer Burden 0/1: 16–17%. Tumors shrink, rarely disappear. Wrong endpoint or wrong combination? @OncoAlert @Larvol https://t.co/U9z38ZdilM
Gaia Griguolo @GaiaGriguolo	Oct 23, 2026	● NEUTRAL	TALENT trial at #ESMO26 Neoadjuvant T-DXd +/- anastrozole or sequentially with TCx4 shows modest activity in HER2-low Hr+ early BC pCR TDXd 7%, TDXd +anastroxole 3%, TDXd x 4 -> TC×4 9% High baseline levels of HER2 prot potentially associated with higher pCR rates @OncoAlert https://t.co/8P5pLJfrg6
Kristina Jankovic, MD @JankovicK	Oct 23, 2026	● NEUTRAL	#TALENT at #ESMO26 🇪🇸 : neoadjuvant T-DXd alone, T-DXd + anastrozole, or T-DXd followed by TC showed high response rates but pCR <10% across all arms in HR+/HER2-low early #BreastCancer Better biomarkers are needed to guide patient selection. @OncoAlert https://t.co/fLXRulAGXD
Philippe Aftimos, MD  @aftimosp	Oct 23, 2026	● NEUTRAL	T-DXd is approved in HER2-low & ultra-low HR+/HER2- MBC after it improved outcomes in pivotal ph3 trials. ❓A role for T-DXd in HER2-low/HR+ early breast cancer? Final resuls from TALENT presented today at #ESMO26 are described & commented by @breastDoktor #ESMOAmbassadors 👇 https://t.co/hzd7KBcJk8
Yakup Ergün @dr_yakupergun	Oct 23, 2026	● NEGATIVE	#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 Amol Akhade @SuyogCancer	Oct 23, 2026	● NEGATIVE	Probably first negative trial for Trastuzumab deruxtecan. Talent trial. For early stage HR positive Her2 low EBC @myESMO #esmo26 @OncoAlert https://t.co/1m62ih9PrE
Paolo Tarantino @PTarantinoMD	Oct 23, 2026	● NEGATIVE	TALENT: neoadjuvant T-DXd, +/- anastrozole or TC, led to a disappointing pCR rate of <10% across arms for HR+ eBC. A hint of superior benefit was observed in patients with high HS-HER2 at baseline. Biomarkers clearly needed to unlock the potential of ADCs in the curative setting. https://t.co/gwUJ6UxMUT
Erika Hamilton, MD, FASCO @ErikaHamilton9	Oct 23, 2026	● NEGATIVE	TALENT- neoadj T-DXd in HR+/HER2-low #bcsm RCB0/1: 🔹 T-DXd alone: 16% 🔹 T-DXd + anastrozole: 17% 🔹 T-DXd → TC chemo: 17% *no pCRs w/out 8 cycles Despite high ORR ~66%, pCR LOW! We know w/ HR+ we don't get high pCRs rates, but still disappointing #ESMO26 #ESMOAmbassadors https://t.co/smlF5DmAAt
Dr Amol Akhade @SuyogCancer	Oct 22, 2026	● NEGATIVE	🚨 ESMO 2026 \| TALENT Trial (LBA23) Disappointing results for neoadjuvant T-DXd in HR+/HER2-low early breast cancer ? 🔹 T-DXd alone: pCR/near-pCR 16% 🔹 T-DXd + anastrozole: 17% 🔹 T-DXd → TC chemotherapy: 17% Despite ORR ~65–67%, pCR rates remained low. Adding endocrine therapy or sequential chemotherapy did not meaningfully improve response. Looking forward towards full dataset. @OncoAlert @myESMO @OncBrothers #ESMO26
Dr Rishabh Jain @DrRishabhOnco	Oct 23, 2026	● NEGATIVE	🚨 TALENT \| #ESMO26 \| LBA23 T-DXd in HR+/HER2-low early breast cancer: Tumors shrink, but pCR remains low! 📊 pCR rates: • T-DXd alone: 7% • + Anastrozole: 3% • → Chemotherapy: 9% ✅ ORR: 65–67% across arms 🔍 Verdict: Encouraging tumor shrinkage, but limited pathologic clearance. No clear benefit from adding endocrine therapy or sequential chemotherapy. Not practice-changing. @ESMO_open @my_esmo @oncoalert #ESMO26 #BreastCancer
Stephanie Graff, MD, FACP, FASCO @DrSGraff	Oct 23, 2026	● NEGATIVE	TALENT—neoadj TDXd (6-8 cycles) +/- AI in HER2 low HR+ early stage breast ca ypCR // RCB TDXd 7% // 16% T-DXd/AI: 3% // 9% T-DXd→ TC: 17% // 17% Author concludes “modest” benefit; I would say “disappointing”. ypCR just isn’t the same endpoint w/ ER+ disease #ESMO26 @OncoAlert https://t.co/3jg6NTqiyH
Yakup Ergün @dr_yakupergun	Oct 23, 2026	● NEGATIVE	#ESMO26 \| TALENT In HR+/HER2-low early breast cancer, neoadjuvant T-DXd ± anastrozole or sequential chemotherapy achieved pCR/near-pCR rates of only 16–17%. Adding anastrozole or sequential chemotherapy showed no clear benefit. https://t.co/pWaagTkKtu https://t.co/KjcRXZkCBd
Kazuki Nozawa, MD @kazuki_nozawa	Oct 23, 2026	● NEGATIVE	TALENT trial #ESMO26 Neoadjuvant T-DXd showed modest efficacy (pCR 3–9%), with limited benefit from additional therapy and potential safety concerns. https://t.co/XCmqAJXtYW
Carmen Criscitiello @CarmenCriscit	Oct 23, 2026	● NEGATIVE	TALENT: neoadjuvant Tdxd in HER2-low, HR+ early breast cancer - modest activity, pCR ~7%, not improved by adding anastrozole or sequencing chemotherapy. A useful reminder that HER2-low is not the same as HER2-driven in the curative setting. #ESMO26 #ESMOAmbassadors @myESMO https://t.co/ajzGVU6sAE
Oncology Brothers @OncBrothers	Oct 23, 2026	● NEGATIVE	3. TALENT: Neoadj TDXd ± AI or → TC in HR+/HER2-low early BC. - pCR: T-DXd 7%; +AI 3%; →TC 9% - Adding ET or seq chemo did not meaningfully improve pCR. Not practice-changing. What does this mean for triple positive mBC? 👇👇 4/8 https://t.co/pjM1GHYOOb https://t.co/VQxclEhYKm
Evandro de Azambuja, MD, PhD @E_de_Azambuja	Oct 23, 2026	● NEGATIVE	Low activity of TDXD in HER2 low ER+ EBC #ESMO26 #ESMOAmbassadors #ESMOcommunity @myESMO https://t.co/OSRlebNcRP
Aydah AlAwadhi, MD 🇦🇪 @Aydah_AlAwadhi	Oct 23, 2026	● NEGATIVE	ESMO 2026 \| TALENT Trial Neoadjuvant T-DXd: modest activity in HR+/HER2-low early breast cancer. pCR rates: T-DXd: 7% T-DXd + anastrozole: 3% T-DXd → chemotherapy: 9% Adding endocrine therapy did not improve pCR, while sequential chemotherapy offered only marginal benefit. ⚠️ 3 cases of grade 2 ILD and 1 patient death. Take-home: Impressive metastatic efficacy has not translated into meaningful neoadjuvant activity. Not practice-changing. #ESMO2026 #BreastCancer #ESMO26 @OncoAlert

Compiled and reviewed by the KOL Pulse research team, led by Brian Shields, Founder, KOL Pulse. Last updated October 23, 2026. Every quote verbatim; every number checked against the ESMO 2026 LBA23 abstract and presentation slides, ClinicalTrials.gov or the FDA, with the source labelled.

TALENT Trial

TALENT Key Takeaways

pCR was low in all three arms

Tumors shrank, but rarely disappeared

Adding anastrozole or chemotherapy did not clearly help

Safety

Regulatory

Top KOLs Discussing TALENT