ESMO Congress 2026

In HR+/HER2− breast cancer, how to sequence treatment after CDK4/6 inhibitors is a central clinical question: relapses after adjuvant CDK4/6i are an emerging challenge, and dedicated studies in this population remain scarce ^[10]; prevailing strategies favor biomarker-driven endocrine choices, with early transition to ADCs such as T-DXd for rapid progression or visceral disease ^[12], and ADCs are regarded as a key component of targeted therapy in this tumor type ^[8]. Against this backdrop, PANKU-Breast01, the phase 3 trial of the EGFR×HER3 bispecific, TOP1-payload ADC izalontamab brengitecan (伦康依隆妥单抗, iza-bren), was ranked first among the must-know top ten abstracts at this ESMO.

Presented as LBA50, the trial was conducted in Chinese patients with HR+/HER2− advanced breast cancer previously treated with endocrine therapy, a CDK4/6 inhibitor, and 1–2 lines of chemotherapy (~70% with 1 prior line). Iza-bren versus physician's choice chemotherapy: median PFS 8.2 vs 4.0 months, HR 0.41 (95% CI 0.33–0.53, p<0.0001), a 59% reduction in the hazard of progression or death; ORR 40.5% vs 20.2%, median DOR 6.9 vs 4.2 months; OS immature. Safety was dominated by hematologic toxicity, with G3+ anemia, neutropenia and thrombocytopenia in ~50% of patients, most patients requiring dose reductions, and primary G-CSF not required; ILD occurred in 1.1%, all grade 1–2.

The portal news reports were consistent with the live data (cORR 40.5%, mPFS 8.2 months, control cORR 20.2%, HR 0.41, ILD 1.1% all grade 1–2) and added information beyond the live posts: the results were presented in the ESMO late-breaking session on 23 October 2026 and simultaneously published in The Lancet; the marketing application for this new indication has been accepted; prior chemotherapy had to include a taxane; the original article notes that OS data are immature and survival benefit is not yet established, and recommends further evaluation in global populations and in earlier lines of HER2-negative breast cancer.

As a step forward, EGFR/HER3 dual targeting frees ADC use from dependence on HER2 expression level, and ORR doubled versus chemotherapy; some on-site commentary judged the efficacy as broadly comparable to DB04 while enrollment was not restricted by HER2 status, while others cautioned that in an era when T-DXd and SG are already in use, superiority over chemotherapy alone is insufficient for positioning, that the added value of dual targeting after prior TOP1-ADCs remains to be proven, and that this meeting also saw phase 3 readouts of other ADCs such as SHR-A1811 and TQB2102 in HER2-low populations ^[2][6]. The limitations are clear: immature OS, evidence from a Chinese population, hematologic toxicity leading to dose reductions in most patients, and sequencing versus existing ADCs all remain to be answered.