Real-world safety and discontinuation rates of fam-trastuzumab deruxtecan in advanced HER2-positive and HER2-low cancer.
Authors: Alqam Anas , Zakhour Joud , Karam Wissam , Ashkar Ryan , Okut Hayrettin , Dakhil Shaker R. , Dakhil Christopher , Mattar Bassam Ibrahim , Koeneke Travis Lee , Moore Dennis Frederic , Moore Joseph A , Truong Phu Van , Truong Quoc Van , Page Seth Joel , Reddy Pavan S. 
Published: July 2024

e12518 Background: Fam-trastuzumab deruxtecan’s (Enhertu) 2022 approval for HER2-low breast cancer spurred widespread adoption of its utilization. DESTINY-Breast04 trial reported 9.9 months median progression-free survival (PFS); however, 16.2% experienced adverse events leading to treatment discontinuation. Our study evaluates real-world adverse event rates causing treatment discontinuation, to assess Enhertu's safety in patients with advanced metastatic cancer. Methods: A retrospective analysis was conducted at a community-based practice in Kansas, USA from 2020 to 2024. 99 patients with HER2-positive and HER2-low cancer, treated with Enhertu, with ECOG performance status of 0 and 1 were identified. Absolute values and proportions were used to represent categorical and nominal variables. Proportions between groups were analyzed using the likelihood ratio chi-square, Fisher's test, and the z-test. Statistical analyses were performed using SAS 9.4. The primary objective was to determine treatment discontinuation rates due to adverse events, while secondary objectives included assessing discontinuation rates due to disease progression, mortality rates, as well as progression-free survival, and dose interruption rates. Results: The average age of patients was 62 years, with 92% being females. The most common cancer types treated were Stage IV metastatic Breast Cancer (87%) and Gastric/Gastroesophageal Junction Cancer (9.1%). Of these cases, 44% were HER2-positive, while the rest were HER2-low. A total of 74% of patients discontinued treatment, with a mean duration of 5.4 months (95% Confidence Interval [CI] 4.2-6.7). Adverse events accounted for 9% of discontinuations, including interstitial lung disease/pneumonitis (33%), thrombocytopenia (11%), diarrhea (11%), nausea (22%), and dysgeusia (11%). 77% experienced grade 2 and 3 adverse events. Disease progression and death resulted in 49.4% and 11% of Enhertu discontinuation respectively. Among patients still on Enhertu (26%), the mean treatment duration was 13.5 months (95% CI 9.5-17.5). The mean PFS was 9.3 months (95% CI 6.2-9.4). Dose interruptions due to adverse events with subsequent resumption occurred in 18% of patients. Conclusions: In our community-based observational study on Enhertu discontinuation rates due to treatment-emergent adverse events (TEAEs), we found a 9% discontinuation rate—significantly lower than the 16.2% reported in the Breast04 trial, (P=0.045). The incidence of interstitial lung disease was 3%, considerably less than the 12% reported in Breast04. Importantly, no deaths related to TEAEs were observed, suggesting a lower occurrence of serious adverse events in clinical practice compared to clinical trials. These results underscore Enhertu's safety profile in advanced metastatic HER2-positive and low cancer.