ESMO Congress 2026

The standing of EGFR as an oncology target was established at the dawn of targeted therapy: activating EGFR mutations in NSCLC correlate with clinical response to gefitinib ^[2][3], and a subsequent phase 3 trial in East Asian patients with advanced pulmonary adenocarcinoma showed gefitinib superior to carboplatin-paclitaxel, with 12-month PFS rates of 24.9% vs 6.7% (HR 0.74) ^[4]. On the breast cancer side, the TCGA multi-platform integrated analysis defined four main molecular classes of breast cancer and identified a HER2/phosphorylated HER2/EGFR/phosphorylated EGFR signature within the HER2-enriched subtype ^[1], indicating EGFR pathway activation in a subset of breast cancers and providing a biological rationale for developing an EGFR/HER3 bispecific ADC in HR+/HER2- breast cancer.

At this meeting, the phase 3 PANKUBREAST01 results took center stage: iza bren (bispecific EGFR/HER3 ADC) versus TPC chemotherapy in previously treated HR+/HER2- metastatic breast cancer, with numbers posted as mPFS 4.0 vs 8.1 months, HR 0.41; ORR 20% vs 40%; DoR 4.2 vs 6.9 months; and ILD only 1.1%, all grade 1/2. A Japanese expert added in the same discussion that iza bren, following TNBC, has again delivered good results in the HR+ population.

Relative to existing knowledge, this readout advances the field by extending the evidence of the EGFR/HER3 dual-target ADC from TNBC into the previously treated HR+/HER2- population, and by providing a safety data point of ILD at only 1.1%, all grade 1/2. A second thread at the venue must also be flagged: the same expert went on to ask whether the efficacy exceeds DATO-DXd, SG and especially T-DXd — acknowledging that cross-trial comparison is not valid — with the personal impression that it may not reach that level, and that expectations rest on combinations and other development strategies. Other scattered EGFR-related items at the meeting: in local therapy, SINDAS was positive in EGFR+ and NRG-LU002 with IO was negative; high GPER and low ESR1/2 expression were significantly associated with outcomes in EGFR-mutant NSCLC; EGFR mutations are more common in women, and women consistently show better survival than men.

Limitations: all figures above are relayed from live conference posts; sample size, OS, subgroup and statistical details were not disclosed; the arm-by-arm correspondence of the ORR and DoR figures needs to be verified against the full dataset (to be confirmed); and the ranking against T-DXd and other ADCs cannot, as the expert noted, be settled by cross-trial comparison — only head-to-head or standardized-control data can.