1766RO
Health-related quality of life from HER2CLIMB-05: A phase 3 study of tucatinib versus placebo in combination with trastuzumab and pertuzumab as 1L maintenance therapy for HER2+ mBC
https://esmocongress.esmo.org
ESMO Congress 2026
October 23–27, 2026 · Madrid · 2949 items
trastuzumab
★★★Late-breaking22 people · 27 posts · 8 abstracts
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Heat now 5·Peak in the comparable set 11 (Oct 23 23:00)·Change over 24h in the comparable set –·Participants now 14
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Deep dive
The evidence base for anti-HER2 therapy has long been established: HER2 amplification or overexpression is seen in 25–30% of breast cancers [1], and trastuzumab is a recombinant antibody designed to block the ErbB2 receptor [4]. Adding trastuzumab to first-line chemotherapy in HER2-positive metastatic breast cancer extended median time to disease progression from 4.6 to 7.4 months [1], and the ToGA trial established trastuzumab plus chemotherapy as the first-line standard in HER2-positive advanced gastric/gastro-oesophageal junction cancer [2]. Per a 2020 review, the only approved targeted options after first-line trastuzumab in gastric cancer were second-line ramucirumab and third-line anti-PD-1, with median survival in advanced disease under 1 year [5] — whether HER2 can still be targeted after trastuzumab progression is exactly where the new data fit in.
The headline update at ESMO26 was KC-WISE, a double-blind phase 3 study enrolling 246 patients with HER2-positive gastric/gastro-oesophageal junction cancer progressed after trastuzumab, randomized to anbenitamab (a biparatopic HER2 bispecific) plus chemotherapy versus placebo plus chemotherapy. Key numbers: ORR 56% vs 14%, median PFS by IRC 7.1 vs 2.7 months, median OS 19.6 vs 9.6 months (HR 0.39, p<0.0001); the trade-off was grade ≥3 TEAEs of 74.2% vs 54.5%.
A parallel readout at the same meeting: trastuzumab rezetecan versus physician's-choice chemotherapy in HER2-low advanced breast cancer improved PFS in both chemo-naive patients and the overall population, with consistent benefit in HR-positive and HR-negative disease, low incidence of ILD, and simultaneous publication in JAMA. Commentators compared it with T-DXd: lower DAR (5.7 vs 8), less ILD but greater myelosuppression, both being HER2-targeted ADCs with a TOP1 inhibitor payload; others cautioned that data for this agent and rolditamig deuderuxtecan came from Chinese populations only, and whether they are better than T-DXd requires head-to-head trials.
The step forward from KC-WISE is straightforward: second-line OS nearly doubled (19.6 vs 9.6 months), showing HER2 remains a valid target after trastuzumab failure and that sequential HER2 blockade works. But the limitations are equally clear: the control arm was single-agent chemotherapy, so the bar was not high; HERIZON has already moved zanidatamab, also biparatopic, to the first line — whether a second biparatopic still works in 2L after one is used up front, or whether that spot goes to T-DXd, was left unanswered at the meeting; and 19.6 months median OS is significantly lower than the 26–27 months seen with HERIZON. On the rezetecan side, head-to-head data versus T-DXd are likewise lacking.
References
- 1.Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2 · N Engl J Med 2001
- 2.Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial · Lancet 2010
- 3.Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials · Lancet 2005
- 4.Untangling the ErbB signalling network · Nat Rev Mol Cell Biol 2001
- 5.Gastric cancer · Lancet 2020
- 6.Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer · N Engl J Med 2005
Evidence
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Safety, social costs and quality of life (QOL) in HER2-positive (HER2+) breast cancer (BC) patients (pts) treated with pertuzumab + trastuzumab fixed-dose combination subcutaneous (PT FDC SC): The PERTURB study
https://esmocongress.esmo.org1795TIP
A global, interventional, open-label trial of trastuzumab deruxtecan (T-DXd)–based therapy in first-line HER2-positive metastatic breast cancer: DESTINY-Breast Guide
https://esmocongress.esmo.org35P
Comparative effectiveness of trastuzumab deruxtecan versus sacituzumab govitecan in HER2-negative metastatic breast cancer: A real-world analysis with propensity score matching
https://esmocongress.esmo.org539RO
Patient-reported outcomes (PROs) from DESTINY-Breast05: Health-related quality of life (HRQoL) with trastuzumab Deruxtecan (T-DXd) versus trastuzumab emtansine (T-DM1) in patients (Pts) with high-risk HER2-positive early breast cancer (eBC)
https://esmocongress.esmo.org543RO
DESTINY-Breast11: MRI-assessed objective responses during neoadjuvant treatment (NAT) with trastuzumab deruxtecan (T-DXd) followed by paclitaxel + trastuzumab + pertuzumab (THP) vs dose-dense doxorubicin + cyclophosphamide followed by THP (
https://esmocongress.esmo.orgLBA13
Trastuzumab rezetecan (SHR-A1811) in HER2-low advanced breast cancer (BC): A randomized, phase 3 study (HORIZON-Breast06)
https://esmocongress.esmo.orgLBA17
HER2-PET imaging to predict trastuzumab deruxtecan (T-DXd) efficacy in advanced breast cancer: The phase II PREDICT-HER trial
https://esmocongress.esmo.orgFloor
Nicholas Hornstein@GIMedOnc China keeps delivering new assets and studies, now in HER2+ gastric 🇨🇳
Evandro de Azambuja, MD, PhD@E_de_Azambuja Elisa Agostinetto@ElisaAgostinett At #ESMO26 proffered paper session 1️⃣ on #breastcancer
Nieves Martinez Lago MD PhD@DraMartinezLago JAMA@JAMA_current JAMA@JAMA_current x.com@ Giampaolo Bianchini@BianchiniGP 🔥 New ADCs in breast cancer, or just more “me-too” ADCs?
Elvina Almuradova@Dr_ElvinaA Stephen V Liu, MD@StephenVLiu Yuhei YAMAGUCHI@yymgcmd Impressive results with trastuzumab rezetecan in the first-line treatment of HR+ MBC!
引用@🇨🇳HORIZON-Breast06: Trastuzumab rezatecan widely outperformed chemo in endocrine-refractory HR+ MBC (PFS 16.6 vs 6.8 months, HR 0.25, p=0<0.01). Definitely passes the truck test. No significant OS, likely due to crossover of some patients to TOPO1 ADCs. #ESMO26 #ESMOAmbassadors
JAMA Oncology@JAMAOnc Presented at #ESMO26 from @JAMA_current:
Dana-Farber News@DanaFarberNews In today’s Clinical Trials Plenary at #AACR26:
Yuhei YAMAGUCHI@yymgcmd 引用@🇨🇳 TQB2102 (biparatopic HER2 TOPO1 ADC) also passes the truck test in mostly HR+/HER2-low MBC. PFS 16.4 vs 5.5 mo, HR 0.29, p<0.01. Unclear whether the biparatopic design adds anything. The HER2 TOPO1 field is getting quite crowded with excellent agents. #ESMOAmbassadors #ESMO26
JAMA+ Trials@JAMAplusTrials Presented at #ESMO26 from @JAMA_current:
JAMA Oncology@JAMAOnc JAMA+ Trials@JAMAplusTrials JAMA+ Women's Health@JAMAWomenHealth Presented at #ESMO26 from @JAMA_current:
JAMA+ Women's Health@JAMAWomenHealth mp.weixin.qq.comPick HORIZON-Breast06 Phase 3: Trastuzumab Rezetecan Extends PFS in HER2-Low Advanced Breast Cancer
The phase 3 HORIZON-Breast06 study of Hengrui Medicine's trastuzumab rezetecan (SHR-A1811) extended progression-free survival in patients with HER2-low advanced breast cancer.
Why it matters: The study provides median PFS, HR and 95% CI for both the chemotherapy-naive and overall populations, enabling quantitative comparison of the ADC against chemotherapy.
clinicaltrials.gov Trastuzumab Rezetecan Followed by Pyrotinib, Fulvestrant, and Dalpiciclib in HR-Positive, HER2-Positive Advanced Breast Cancer
medRxiv Oncology Adjuvant Trastuzumab Deruxtecan Versus Trastuzumab Emtansine by Residual Cancer Burden in HER2-Positive Early Breast Cancer: A Decision Analysis
medRxiv Oncology Nationwide HER2 Testing, Prospective Trastuzumab-Based Therapy, and Deep Visual Proteomics in Esophageal Squamous Cell Carcinoma
clinicaltrials.gov BL-M07D1 (Trastuzumab Brengitecan T-bren) vs Standard of Care Platinum-based Chemotherapy (PBC) for HER2-expressing Metastatic Urothelial Cancer After Progression on Anti-PD-(L)1-based Therapy
A newly registered phase 3 trial (NCT07869836) will randomize 520 participants with HER2-expressing metastatic urothelial cancer progressing on or after anti-PD-(L)1-based therapy to BL-M07D1 (trastuzumab brengitecan, T-bren) at one of two dose levels versus gemcitabine plus platinum-based chemotherapy (cisplatin or carboplatin). Sponsored by SystImmune, it is recruiting with a planned start in September 2026 and will evaluate efficacy and safety.
bioRxiv Cancer BiologyPick Trastuzumab deruxtecan kills skin and uveal melanoma in vivo by HER2-independent payload release
Trastuzumab deruxtecan (T-DXd) inhibited all subcutaneous melanoma PDXs and outperformed trastuzumab emtansine (T-DM1), which had limited activity, while liver models were less sensitive. Parental and ERBB2-knockout xenografts responded similarly at first, though knockout tumors regrew earlier, and melanoma cells resisted both ADCs in vitro with little trastuzumab uptake. Tumor-derived cathepsin L found outside melanoma cells suggests payload release can occur extracellularly, independent of HER2.
Why it matters: Suggests T-DXd may work in melanoma through HER2-independent payload cleavage, widening its potential use beyond HER2-positive tumors.
mp.weixin.qq.com Trastuzumab Deruxtecan Wins Tumor-Agnostic Approval in China, Its Tenth Indication
Trastuzumab deruxtecan received its tenth indication in China on October 20, for adults with unresectable or metastatic solid tumors expressing HER2 at IHC 3+ who have received prior treatment or have no satisfactory alternative treatment options. It is the first HER2-targeted ADC approved for a tumor-agnostic indication in China.
mp.weixin.qq.comPick ESMO 2026 Breast Cancer ADC Rapid Orals Cover Neoadjuvant Therapy, Overall Survival and Resistance Sequencing
Liangyihui compiles seven rapid oral reports on breast cancer ADCs from ESMO 2026, covering neoadjuvant treatment in HER2-positive early breast cancer, overall survival in metastatic TNBC, sequential strategies after ADC resistance, and clinical data on ADCs with novel targets.
Why it matters: Compiles multiple ESMO 2026 breast cancer ADC oral reports spanning early neoadjuvant therapy, late-line survival benefit, resistance sequencing, and China-developed data.
Same topic trastuzumab · 28 peopleNo engagement yetmp.weixin.qq.comPick Trastuzumab Deruxtecan Receives Conditional Tumor-Agnostic HER2 Approval in China
Trastuzumab deruxtecan (Enhertu) has received conditional approval in China as monotherapy for adults with unresectable or metastatic solid tumors expressing HER2 at IHC 3+ who have received prior treatment or have no satisfactory alternative options. The approval is based on four phase II trials: DESTINY-PanTumor02, DESTINY-Lung01, DESTINY-CRC02 and DESTINY-PanTumor03, with full approval contingent on clinical benefit demonstrated in confirmatory trials.
Why it matters: Four phase II trials supply ORR, PFS, OS and safety data across tumor types and identify the confirmatory trials underpinning conditional approval.
mp.weixin.qq.comPick Trastuzumab Deruxtecan Gains Conditional Tumor-Agnostic HER2-Positive Approval in China
Daiichi Sankyo's trastuzumab deruxtecan (Enhertu) has been approved in China for adult patients with unresectable or metastatic solid tumors expressing HER2 IHC 3+ who have received prior treatment or have no satisfactory alternative options. The approval, granted conditionally by the NMPA, covers a tumor-agnostic indication.
Why it matters: Four phase II studies provide cross-tumor ORR, survival and ILD safety data for weighing benefit, risk and evidence limits.
mp.weixin.qq.comPick Daiichi Sankyo and AstraZeneca's Trastuzumab Deruxtecan Wins Tumor-Agnostic Indication in China
On October 22, Daiichi Sankyo and AstraZeneca's trastuzumab deruxtecan received approval in China for a new tumor-agnostic indication: adults with unresectable or metastatic HER2 IHC 3+ solid tumors who have received prior treatment or have no satisfactory alternative options. The CDE had granted the indication priority review. Since its first approval in December 2019, the drug has expanded across breast cancer, gastric cancer and non-small cell lung cancer, among other tumor types.
Why it matters: Trastuzumab deruxtecan's HER2 IHC 3+ tumor-agnostic approval in China allows comparison of review timing and covered populations with analogous global approvals.
Same topic trastuzumab · 40 peopleNo engagement yet