ESMO 2026 breast cancer round-up: What are the key findings for clinical practice?

New survival data and emerging treatment strategies take center stage at ESMO 2026, with seven key studies exploring adjuvant CDK4/6 inhibition, treatment sequencing in advanced disease and the expanding role of antibody–drug conjugates

The European Society for Medical Oncology (ESMO) Congress 2026 brought new evidence across early and advanced breast cancer, with important updates on endocrine-based treatment, targeted therapies and ADCs. The selected studies examine several key questions in clinical practice, including the long-term benefits of adjuvant treatment, therapeutic options following progression on CDK4/6 inhibitors and the potential of emerging ADCs to improve outcomes in advanced disease.

NATALEE: Six-year overall survival and efficacy outcomes with adjuvant ribociclib

Abstract: LBA25 | ClinicalTrials.gov: NCT03701334 | Phase: III

The phase III NATALEE trial evaluated adjuvant ribociclib (RIB) plus a nonsteroidal aromatase inhibitor (NSAI) versus NSAI alone in patients with high-risk stage II/III hormone receptor-positive (HR+)/HER2-negative early breast cancer (EBC). The latest prespecified analysis reports overall survival (OS) and efficacy outcomes after 6 years of follow-up. At a median OS follow-up of 66.5 months, RIB plus NSAI demonstrated an OS benefit over NSAI alone (hazard ratio [HR], 0.809; 95% confidence interval [CI], 0.661–0.989; nominal one-sided P=.019). The absolute OS benefit increased from 1.2% at 5 years (93.89% vs 92.73%) to 2.1% at 6 years (91.86% vs 89.73%). Invasive disease-free survival (iDFS) benefit was also maintained (HR, 0.741; 95% CI, 0.646–0.849; nominal one-sided P<.0001), with the absolute difference increasing from 4.1% at 5 years (85.32% vs 81.24%) to 5.3% at 6 years (83.23% vs 77.92%). Benefits in breast cancer-specific survival (BCSS; HR, 0.706; 95% CI, 0.559–0.890), distant disease-free survival (DDFS; HR, 0.744; 95% CI, 0.646–0.858) and distant recurrence-free survival (DRFS; HR, 0.738; 95% CI, 0.634–0.858) were also maintained. At the data cutoff, all patients had been off RIB for a median of 38 months and had progressed beyond the predefined NSAI study regimen. No new safety signals were observed.

Key clinical takeaway: The six-year results demonstrate sustained reductions in recurrence risk and a nominally significant OS benefit with adjuvant ribociclib plus NSAI. The findings provide further evidence supporting adjuvant CDK4/6 inhibition in patients with high-risk stage II/III HR+/HER2− EBC.

FOURLIGHT-1: Atirmociclib plus fulvestrant following progression on CDK4/6 inhibitors

Abstract: 1842O | ClinicalTrials.gov: NCT06105632 | Phase: II

FOURLIGHT-1 investigated atirmociclib (ATI), a next-generation cell cycle inhibitor highly selective for CDK4, plus fulvestrant (FUL) in patients with HR+/HER2− advanced or metastatic breast cancer (mBC) who had progressed on previous CDK4/6 inhibitor therapy. The open-label, randomized phase II study compared ATI plus FUL with investigator’s choice of standard therapy (ICT), comprising FUL alone or everolimus (EVE) plus exemestane (EXE). Among 263 patients, ATI plus FUL significantly improved investigator-assessed progression-free survival (PFS) compared with ICT (median, 9.4 vs 6.6 months; HR, 0.60; 95% CI, 0.440–0.825; one-sided P=0.0007). Among patients with measurable disease, objective response rates (ORRs) were 19.3% (21/109) and 11.3% (13/115), respectively. Median duration of response (DOR) was 14.8 versus 9.3 months, while clinical benefit rates (CBRs) were 61.9% versus 46.0%. Overall survival (OS) data were not yet mature. The most common treatment-related adverse events (TRAEs) with ATI were neutropenia (46.4%) and leukopenia (32.8%), and 4.0% of patients discontinued ATI due to TRAEs.

Key clinical takeaway: FOURLIGHT-1 provides phase II evidence for a next-generation selective CDK4 inhibitor following progression on previous CDK4/6 inhibitor therapy. The significant PFS improvement supports further investigation of this approach, including in earlier treatment lines.

postMONARCH: Final overall survival analysis of abemaciclib plus fulvestrant

Abstract: 1RO | ClinicalTrials.gov: NCT05169567 | Phase: III

The phase III postMONARCH trial evaluated abemaciclib plus fulvestrant versus placebo plus fulvestrant in patients with HR-positive/HER2-negative advanced breast cancer following progression on a previous CDK4/6 inhibitor plus endocrine therapy (ET). Among 368 randomized patients, the final OS analysis showed numerically longer median OS with abemaciclib plus fulvestrant compared with placebo plus fulvestrant (32.1 vs 24.6 months; HR, 0.80; 95% CI, 0.60–1.06; P=0.1145). However, the difference did not reach statistical significance. Updated PFS remained consistent with the primary analysis (HR, 0.78; 95% CI, 0.62–0.99; nominal P=0.0390). Time to second progression and chemotherapy-free survival also favored abemaciclib. No new safety signals were identified.

Key clinical takeaway: Although the final OS analysis did not meet the prespecified significance threshold, the findings provide additional information on continued CDK4/6 inhibition following disease progression. The results should be interpreted alongside the statistically significant PFS findings and the overall evidence for treatment sequencing in advanced HR-positive/HER2-negative disease.

PANKU-BREAST01: Izalontamab brengitecan following previous treatment in HR-positive/HER2-negative advanced breast cancer

Abstract: LBA50 | ClinicalTrials.gov: NCT06343948 | Phase: III

PANKU-BREAST01 evaluated izalontamab brengitecan (iza-bren), a first-in-class bispecific ADC targeting EGFR and HER3 and containing a topoisomerase I inhibitor payload (Ed-04), in patients with previously treated unresectable locally advanced or metastatic HR+/HER2− breast cancer. The randomized phase III study compared iza-bren with treatment of physician’s choice (TPC), comprising eribulin, capecitabine, gemcitabine or vinorelbine. Among 383 randomized patients, iza-bren significantly improved PFS by blinded independent central review (BICR) compared with TPC (median, 8.18 vs 4.01 months; HR, 0.41; 95% CI, 0.33–0.53; P<0.0001). The confirmed ORR was 40.5% versus 20.2%, while median duration of response was 6.93 versus 4.21 months. OS data were immature at the interim analysis. Grade ≥3 TRAEs were predominantly hematologic, and interstitial lung disease (ILD) occurred in 2 patients (1.1%) receiving iza-bren. Only 1.6% of patients discontinued iza-bren due to TRAEs.

Key clinical takeaway: Iza-bren significantly improved PFS compared with chemotherapy in previously treated HR+/HER2− advanced breast cancer. The findings support further evaluation of this bispecific ADC, although the current results relate to a population treated in China and OS data remain immature.

APEX-BREAST01: TQB2102 versus chemotherapy in HER2-low recurrent or metastatic breast cancer

Abstract: LBA27 | ClinicalTrials.gov: NCT06561607 | Phase: III

APEX-BREAST01 investigated TQB2102, a novel biparatopic HER2-targeting ADC, versus chemotherapy in patients with HER2-low recurrent or metastatic breast cancer who had not received previous chemotherapy for advanced disease. Patients with HR-positive disease had to have progressed after at least one line of endocrine therapy for metastatic disease. The primary endpoint was PFS by BICR in patients with HR-positive/HER2-low disease. Among 543 randomized patients, median PFS was significantly longer with TQB2102 than with TPC in the HR-positive population (16.4 vs 5.5 months; HR, 0.29; 95% CI, 0.22–0.39; P<0.0001). The benefit was also observed across the overall HER2-low population, with median PFS of 16.4 versus 5.5 months (HR, 0.29; 95% CI, 0.22–0.38; P<0.0001). ORRs were 66.7% versus 31.3% in HR-positive patients and 68.8% versus 31.0% in the overall HER2-low population. OS data were immature, although a favorable trend was reported. The most common grade ≥3 TRAEs were decreased neutrophil count (30.1% vs 23.3%) and decreased white blood cell count (21.6% vs 14.0%). TQB2102-related ILD occurred in 6 patients (2.2%), including grade 3 events in 1.1%. TRAEs led to treatment discontinuation in 1.5% of patients in each group.

Key clinical takeaway: TQB2102 demonstrated a substantial PFS improvement over chemotherapy in this phase III study, including among patients with HR-positive/HER2-low disease. The results add to the emerging evidence for ADCs in HER2-low breast cancer, although longer follow-up is needed to establish OS outcomes and further characterize safety.

HORIZON-BREAST06: Trastuzumab rezetecan in HER2-low advanced breast cancer

Abstract: LBA13 | ClinicalTrials.gov: NCT05814354 | Phase: III

HORIZON-BREAST06 evaluated trastuzumab rezetecan (SHR-A1811), a HER2-targeting ADC, versus physician’s choice of chemotherapy in patients with HER2-low advanced breast cancer who had received one or fewer previous lines of chemotherapy for metastatic disease. Previous endocrine therapy was required for patients with HR-positive disease. Among 551 randomized patients, trastuzumab rezetecan significantly improved PFS by BICR in both chemotherapy-naive patients (median, 16.6 vs 6.8 months; HR, 0.25; 95% CI, 0.19–0.33; P<0.0001) and the overall population (median, 16.4 vs 6.8 months; HR, 0.27; 95% CI, 0.21–0.34; P<0.0001). The benefit was consistent across HR-positive and HR-negative subgroups. OS data remained immature, with a trend favoring trastuzumab rezetecan. Grade ≥3 treatment-related adverse events occurred in 84.1% of patients receiving trastuzumab rezetecan compared with 67.9% receiving chemotherapy. ILD was reported in 7 patients (2.5%) in the trastuzumab rezetecan group.

Key clinical takeaway: Trastuzumab rezetecan significantly improved PFS compared with chemotherapy in HER2-low advanced breast cancer, with consistent findings across HR subgroups and chemotherapy-naive and overall populations. The high incidence of grade ≥3 treatment-related adverse events is an important consideration when assessing the results.

DESTINY-Breast09: Intracranial activity of trastuzumab deruxtecan plus pertuzumab in patients with baseline brain metastases

Abstract: LBA49 | ClinicalTrials.gov: NCT04784715 | Phase: III

This exploratory analysis of DESTINY-Breast09 evaluated the intracranial efficacy of trastuzumab deruxtecan (T-DXd) plus pertuzumab (P) compared with taxane, trastuzumab and pertuzumab (THP) in patients with previously untreated HER2-positive advanced or metastatic breast cancer and baseline brain metastases (BMs). Among 61 patients with baseline BMs assessed by BICR who had at least one post-baseline brain scan (T-DXd plus P, n=31; THP, n=30), median PFS was 36.5 months with T-DXd plus P versus 11.1 months with THP. Median central nervous system PFS (CNS-PFS) was not estimable (NE) with T-DXd plus P compared with 9.7 months with THP (HR, 0.26; 95% CI, 0.11–0.57). The CNS-confirmed objective response rate (CNS-cORR) was 51.6% versus 26.7%, respectively. Median CNS duration of response (CNS-DOR) was also not estimable with T-DXd plus P compared with 18.5 months with THP. These findings were observed in an exploratory analysis with a relatively small patient population.

Key clinical takeaway: The analysis provides additional evidence of intracranial activity with first-line T-DXd plus pertuzumab in HER2-positive advanced breast cancer. The findings are relevant to treatment decisions for patients with brain metastases, although the small subgroup size and exploratory nature of the analysis should be considered when interpreting the results.

This content has been developed independently by Touch Medical Media for touchONCOLOGY. It is not affiliated with the European Society for Medical Oncology (ESMO). Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media. This article was created by the editorial team utilizing AI as an editorial tool (Claude.AI and ChatGPT 5.5). The content was developed and edited by human editors. No funding was received in the publication of this article.

Cite: ESMO 2026 breast cancer round-up: What are the key findings for clinical practice? touchONCOLOGY. 5th November 2026.

Editor: Sophie Nickelson