NATALEE 6-Year OS Data and Novel ADCs in Breast Cancer Take Center Stage at ESMO 2026

Breast Cancer Briefing, hosted by Sara Nunnery, MD, MSCI, a breast medical oncologist and the director of Breast Cancer Research at Tennessee Oncology in Nashville, is a podcast series that breaks down the latest news in breast cancer research, one conversation at a time.

In this episode, Dr Nunnery sat down with Sarah Premji, MD, a breast medical oncologist at Sarah Cannon Research Institute Oncology Partners and the assistant director of breast cancer research at Sarah Cannon Research Institute in Nashville, Tennessee.

The experts discussed key breast cancer data presented at the 2026 ESMO Congress, beginning with the 6-year analysis of the phase 3 NATALEE trial (NCT03701334). Dr Premji explained that adjuvant ribociclib (Kisqali) plus endocrine therapy continued to generate an invasive disease–free survival benefit vs endocrine therapy alone in patients with hormone receptor–positive, HER2-negative early breast cancer, and that a descriptive overall survival benefit also held promise. Although this analysis was nominal and not alpha controlled, she characterized the efficacy findings as clinically meaningful and consistent with findings from the phase 3 monarchE trial (NCT03155997) of abemaciclib (Verzenio) plus endocrine therapy in this patient population. The conversation then compared the 2 CDK4/6 inhibitors, including considerations for treatment duration, gastrointestinal toxicity associated with abemaciclib, QT prolongation seen with ribociclib, step-up dosing, and reassurance about dose reductions.

Turning to antibody-drug conjugates, Drs Nunnery and Premji reviewed approved agents and their targets and payloads, highlighting data suggesting that cross-resistance between antibody-drug conjugates (ADCs) with the same topoisomerase I inhibitor payload may limit sequential benefit. They then examined 3 novel ADCs. In the phase 3 HORIZON-Breast06 trial (NCT05814354) in patients with HER2-low metastatic disease, the HER2-directed ADC trastuzumab rezetecan (SHR-A1811) improved median progression-free survival vs chemotherapy. In the phase 3 APEX-Breast01 trial (NCT06561607), the biparatopic HER2-directed ADC TQB2102 yielded a median progression-free survival (PFS) improvement vs chemotherapy in HER2-low recurrent or metastatic disease. Finally, the EGFR/HER3 bispecific ADC izalontamab brengitecan (BL-B01D1) improved the median PFS vs chemotherapy in heavily pretreated patients with hormone receptor–positive, HER2-negative disease in the phase 3 PANKU-Breast01 trial (NCT06343948). Dr Premji emphasized that future trials should use ADCs as comparators and that novel payloads are needed.