ADCs, and Metabolic Health Strategies, and Lifestyle Interventions Add up to Holistic TNBC Care: With Chandler Park, MD; and Neil M. Iyengar, MD

In this episode of Oncology Unplugged, host Chandler Park, MD, a medical oncologist at Norton Cancer Institute in Louisville, Kentucky, was joined by Neil M. Iyengar, MD, an associate professor and co-director of Breast Medical Oncology in the Department of Hematology and Medical Oncology at the Emory University School of Medicine, as well as the director of Survivorship Services at the Winship Cancer Institute of Emory University in Atlanta, Georgia.

Their conversation focused on the rapidly evolving treatment paradigm for triple-negative breast cancer (TNBC), the integration of metabolic health strategies, the clinical emergence of antibody-drug conjugates (ADCs) in the frontline metastatic setting, and the management of treatment-related toxicities.

Drs Park and Iyengar examined data from the phase 3 TROPION-Breast02 trial (NCT05374512), which evaluated first-line datopotamab deruxtecan-dlnk (Dato-DXd; Datroway) in patients with PD-L1-negative metastatic TNBC. The trial demonstrated improvements in both progression-free survival and overall survival (OS) with Dato-DXd compared with standard chemotherapy. Notably, the experts also highlighted a remarkable ORR with Dato-DXd, showing that the ADC may be a robust treatment option for symptomatic patients or those experiencing rapid progression.

They also discussed individualizing treatment between Dato-DXd and sacituzumab govitecan-hziy (Trodelvy) based on biomarker status, dosing schedules, and distinct toxicity profiles. Furthermore, the experts emphasized the importance of proactive management of unique ADC-associated toxicities. For Dato-DXd, they recommended prophylactic dexamethasone mouthwash and lubricating eye drops to mitigate mucositis and corneal surface events. For sacituzumab govitecan, they noted the necessity of growth factor support for neutropenia and loperamide for diarrhea.

Regarding early-stage disease, they reaffirmed the phase 3 KEYNOTE-522 trial (NCT03036488) regimen of pembrolizumab (Keytruda) plus chemotherapy as the standard of care, with adjuvant escalation using capecitabine or PARP inhibitors for patients with residual disease.

Drs Park and Iyengar concluded by spotlighting metabolic health interventions for patients with breast cancer. Although GLP-1 receptor agonists show promise in breast cancer survivors, Dr Iyengar cautioned against their initiation during active neoadjuvant immunotherapy due to their potential effects on pathologic complete response rates. He advocated for lifestyle interventions, including resistance training and a plant-forward, high-protein diet, to maintain lean muscle mass and improve OS outcomes.