Advancements in breast cancer therapeutics took center stage at the 2024 European Society for Medical Oncology (ESMO) Congress, with new data emerging for antibody-drug conjugates (ADCs) and molecular therapies. Several trials presented practice-changing results and important updates in novel treatment development.
KEYNOTE-522: Pembrolizumab in Early-Stage TNBC
The final overall survival data from the phase 3 KEYNOTE-522 trial (NCT03036488) confirmed the benefit of adding pembrolizumab (Keytruda) to neoadjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC). At a median follow-up of 75.1 months, 14.7% of patients in the pembrolizumab arm died compared to 21.8% in the control arm (HR, 0.66; 95% CI, 0.50-0.87; P = .0015). The 5-year overall survival (OS) rates were 86.6% vs 81.7%. The 5-year event-free survival rate was 81.2% in the pembrolizumab arm vs 72.2% in the placebo arm (HR, 0.65; 95% CI, 0.51-0.83).
Peter Schmid, MD, PhD, of Barts Cancer Institute in London, noted that these results support the use of neoadjuvant chemotherapy and perioperative pembrolizumab as standard care for this patient group.
NATALEE: Ribociclib in High-Risk Primary Breast Cancer
The 4-year update from the NATALEE trial (NCT03701334) of adjuvant ribociclib (Kisqali) for high-risk primary breast cancer demonstrated a significant improvement in invasive disease-free survival (iDFS). The phase 3 trial showed that adding ribociclib to adjuvant aromatase inhibition for stage II and III hormone receptor–positive early breast cancer led to an iDFS benefit (HR, 0.715; 95% CI, 0.609-0.840; P < .001). With a median follow-up time of 44.2 months, ribociclib added a 4-year absolute iDFS improvement of 4.9%, an increase from the previously presented improvement of 2.7% at 3 years. The 4-year absolute iDFS benefit was 5.1% in the N0 population and 5.0% in the N+ population. Based on these data, ribociclib plus endocrine therapy received FDA approval for adjuvant use on September 17, 2024.
DESTINY-Breast12: Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer with Brain Metastases
The DESTINY-Breast12 trial (NCT04739761) was a phase 3b/4 multicenter trial evaluating trastuzumab deruxtecan (T-DXd; Enhertu) in patients with HER2-positive metastatic breast cancer who had received up to 2 lines of therapy in the metastatic setting and had stable or active brain metastases. In patients with brain metastases, the 12-month progression-free survival (PFS) rate was 61.6% (95% CI, 54.9%-67.6%) and the 12-month central nervous system PFS was 58.9% (95% CI, 51.9%-65.3%). The rates were similar in patients with stable (57.8%; 95% CI, 48.2%-66.1%) and active (60.1%; 95% CI, 49.2%-69.4%) brain metastases. These results demonstrated significant intracranial activity of T-DXd.
ICARUS-BREAST01: Patritumab Deruxtecan in HR+/HER2- Advanced Breast Cancer
Phase 2 results from the ICARUS-BREAST01 trial (NCT04965766) testing the novel HER3-directed ADC patritumab deruxtecan (HER3-DXd) were presented. Patients with hormone receptor–positive, HER2-negative metastatic breast cancer who had progression on CDK4/6 inhibitor and 1 line of chemotherapy were enrolled. At a median follow-up of 15.3 months, the confirmed objective response rate was 53.5% (95% CI, 43.2%-63.6%) and the median PFS was 9.4 months (95% CI, 8.1-13.4). These results support the continued development of this novel ADC.
Additional Studies
Additional studies presented at ESMO 2024 highlighted the beneficial effects of exercise on symptom management, quality of life, and improvements in invasive breast cancer–free survival and OS with high-intensity interval training plus resistance training during chemotherapy for early breast cancer.
