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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 · 3061 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
mp.weixin.qq.comPick FDA Approves Pfizer's TUKYSA Plus Trastuzumab and Pertuzumab for First-Line HER2+ Breast Cancer Maintenance
The FDA approved Pfizer's TUKYSA (tucatinib) combined with trastuzumab and pertuzumab as maintenance therapy after induction treatment for adults with unresectable locally advanced or metastatic HER2-positive breast cancer. The approval extends TUKYSA into the first-line setting and offers a chemotherapy-free maintenance option. According to Pfizer, the regimen reduced the risk of death by 35.9% compared with trastuzumab alone.
Why it matters: FDA approval moves Pfizer's TUKYSA into first-line HER2+ breast cancer maintenance with a 35.9% death-risk reduction.
clinicaltrials.gov Response-Guided Bladder Preservation With Trastuzumab Rezetecan, Adebrelimab, and Concurrent Bladder Radiotherapy in HER2-Expressing Muscle-Invasive Bladder Cancer
FDA DrugsPick FDA approves tucatinib with trastuzumab and pertuzumab for the maintenance treatment of HER2-positive breast cancer
The FDA approved tucatinib (Tukysa, Seagen, a Pfizer subsidiary) with trastuzumab and pertuzumab on October 7, 2026, for maintenance treatment of adults with unresectable locally advanced or metastatic HER2-positive breast cancer after induction therapy. In the 654-patient HER2CLIMB-05 trial, median progression-free survival was 24.9 months with tucatinib 300 mg twice daily versus 16.3 months with placebo (HR 0.64, p<0.0001). The label carries a boxed warning for hepatotoxicity; overall survival data were immature.
Why it matters: FDA approval extends tucatinib to first-line maintenance, with PFS results from a randomized phase 3 trial.
clinicaltrials.gov Trastuzumab/Pertuzumab With Fulvestrant and Kurmoxilil in HR+/HER2+ Early Breast Cancer
clinicaltrials.gov SHR-A1811 Versus Trastuzumab Plus Pertuzumab in ctDNA-Positive HER2-Positive Early Breast Cancer After Pathologic Complete Response
Nat Med Evorpacept plus trastuzumab, ramucirumab and paclitaxel in HER2-positive gastric cancer: a randomized phase 2 trial.
Nat Med Trastuzumab plus nivolumab with gemcitabine and cisplatin as first-line therapy for HER2-positive unresectable biliary tract cancer: a phase 1b/2 trial.
Nature MedicinePick Evorpacept plus trastuzumab, ramucirumab and paclitaxel in HER2-positive gastric cancer: a randomized phase 2 trial
Adding the CD47 inhibitor evorpacept to trastuzumab, ramucirumab and paclitaxel (TRP) produced a higher objective response rate than TRP alone in patients with HER2-positive advanced gastric cancer that had progressed on anti-HER2 treatment. The finding comes from the phase 2 part of the randomized ASPEN-06 trial. Response was associated with CD47 and HER2 expression.
Why it matters: It tests CD47 blockade as a way to overcome resistance to anti-HER2 therapy in gastric cancer.
Nature MedicinePick Trastuzumab plus nivolumab with gemcitabine and cisplatin as first-line therapy for HER2-positive unresectable biliary tract cancer: a phase 1b/2 trial
A phase 1b/2 trial tested trastuzumab combined with nivolumab, gemcitabine and cisplatin as first-line therapy for HER2-positive unresectable biliary tract cancer. The regimen showed encouraging clinical response rates, and HER2 expression was associated with clinical benefit. The results support HER2 status as a marker guiding trastuzumab-based treatment in this population.
Why it matters: First data on adding trastuzumab and nivolumab to standard gemcitabine-cisplatin in HER2-positive biliary tract cancer.
mp.weixin.qq.comPick Trastuzumab Deruxtecan Extends Median PFS to 14.3 Months as First-Line Therapy in HER2-Mutant Advanced NSCLC
In the phase III DESTINY-Lung04 trial, first-line trastuzumab deruxtecan (Enhertu) gave a median progression-free survival of 14.3 months in patients with HER2-mutant advanced non-small cell lung cancer, versus 8.3 months with pembrolizumab plus chemotherapy. It is the first HER2-targeted therapy to show superiority over standard treatment in this setting.
Why it matters: First HER2-targeted therapy to beat standard first-line care in HER2-mutant advanced NSCLC in phase III.
N Engl J Med Advances in Systemic Treatment of Breast Cancer.
A New England Journal of Medicine review traces systemic therapy for breast cancer since 2020, covering targeted therapies, antibody-drug conjugates and immunotherapy across biologic subtypes. CDK4/6 inhibitors remain foundational in hormone-receptor-positive, HER2-negative disease, trastuzumab deruxtecan is reshaping HER2-positive treatment, and immune checkpoint inhibitors have improved outcomes in triple-negative breast cancer. Unresolved issues include treatment sequencing, predictive biomarkers, circulating tumor DNA analysis and equitable access to high-cost therapies.
Same topic trastuzumab · 28 peopleNo engagement yetmedRxiv Oncology Multimodal Artificial Intelligence Predicts Pathological Response and Prognosis in HER2-Positive Early Breast Cancer Treated with Chemotherapy De-escalation Strategies: Analyses from PHERGain and PHERGain-2 Trials
medicalxpress.comPick Tumor markers reveal which HER2+ breast cancer patients may respond to less intensive chemotherapy
In the CompassHER2-pCR trial, 43.8% of 2,141 early-stage HER2-positive breast cancer patients achieved a pathologic complete response after 12 weeks of neoadjuvant taxane, trastuzumab and pertuzumab, rising to 63.7% in ER-negative disease. The HER2DX test, analyzed in 569 participants, showed pCR rates of 68% with high scores versus 19% with low scores, an association that held after adjustment for clinical factors. The results support using tumor markers to select patients for less intensive chemotherapy.
Why it matters: It identifies predictors of response to de-escalated chemotherapy in early-stage HER2+ breast cancer.
pubmed.ncbi.nlm.nih.gov Super-antifouling electrochemical biosensor based on a biomimetic gemini zwitterionic interface for sensitive detection of therapeutic antibodies
Same topic trastuzumab · 28 peopleNo engagement yetmp.weixin.qq.comPick NMPA Approves Hengrui HER2 ADC Ruikang Trastuzumab for HER2-Positive Colorectal Cancer
NMPA approved a new indication for Hengrui Medicine's HER2 ADC ruikang trastuzumab (Aivida) on August 6 for adults with HER2-positive colorectal cancer who failed prior oxaliplatin, fluorouracil and irinotecan treatment. It becomes China's first targeted therapy specifically for HER2-positive colorectal cancer. The pivotal study showed nearly doubled progression-free survival and an overall response rate of 40.7%.
Why it matters: First approved targeted therapy for HER2-positive colorectal cancer in China, from a pivotal study readout.