Adopting Best Practices for Administering TROP2-Directed ADCs in NSCLC

In the third edition of a special podcast series, CancerNetwork^® spoke with Daniel Morgensztern, MD; Mary Ellen Flanagan, NP; and Janelle Mann, PharmD, BCOP, about optimal strategies for incorporating different therapeutic agents into lung cancer care. As part of the latest discussion, the group highlighted the relevant efficacy data, administration protocols, and toxicity management considerations associated with TROP2-directed antibody-drug conjugates (ADCs) in patients with non–small cell lung cancer (NSCLC).

Morgensztern is a professor of Medicine and the clinical director of Thoracic Oncology in the Division of Oncology at Washington University School of Medicine in St. Louis. Flanagan is a nurse practitioner in the Division of Thoracic Oncology at Washington University. Mann is a clinical oncology pharmacist at Siteman Cancer Center of Washington University School of Medicine and manager of Clinical Pharmacy Services at Barnes-Jewish Hospital.

Morgensztern opened the discussion by highlighting the characteristics of prominent TROP2-targeting ADCs in NSCLC management, which included sacituzumab govitecan-hziy (Trodelvy), datopotamab deruxtecan-dlnk (Datroway), and sacituzumab tirumotecan (sac-TMT). Additionally, he reviewed data from clinical trials assessing these ADCs across different NSCLC populations, including the phase 3 EVOKE-01 trial (NCT05089734) showing a numerical overall survival (OS) improvement with sacituzumab govitecan vs docetaxel.

Regarding the safety profiles of these ADCs, Flanagan described the unique toxicities associated with the agents’ payloads as well as potential off-target effects. On top of myelosuppression, fatigue, and diarrhea, she stated that these therapies may cause more visceral organ toxicities like keratitis of the eye and interstitial lung disease. According to Flanagan, some prophylactic measures in the event of certain toxicities include frequent salt and baking soda mouth rinses as well as oral dexamethasone.

Mann then outlined the dosing variability considerations and supportive care measures surrounding the use of agents like sacituzumab govitecan. She emphasized continuously re-educating patients about expected toxicities and supportive care strategies as they undergo these infusion-based therapies to help avoid surprise instances of ocular toxicity, diarrhea, and other adverse effects.

Reference

Paz-Ares LG, Juan-Vidal O, Mountzios GS, et al. Sacituzumab govitecan versus docetaxel for previously treated advanced or metastatic non-small cell lung cancer: the randomized, open-label phase III EVOKE-01 study. J Clin Oncol. 2024;42(24):2860-2872. doi:10.1200/JCO.24.00733