Efficacy of administration sequence: Sacituzumab Govitecan and Trastuzumab Deruxtecan in HER2-low metastatic breast cancer
Menée à partir de données portant sur 179 patientes atteintes d'un cancer métastatique du sein exprimant faiblement HER2, cette étude multicentrique rétrospective évalue l'efficacité, du point de vue de la survie sans progression, d'une administration séquentielle de sacituzumab govitécan et de trastuzumab déruxtécan avec ou sans ligne intermédiaire de chimiothérapie
Background: Current guidelines recommend that patients with HER2-low metastatic breast cancer (MBC) receive sequentially two antibody–drug conjugates (ADCs): Sacituzumab Govitecan (SG) and Trastuzumab Deruxtecan (T-DXd), despite a similar payload. However, the effectiveness of one after another is unknown.
Methods: ADC-Low is a multicentre, retrospective study evaluating the efficacy of SG and T-DXd, one after another, with or without intermediary lines of chemotherapy, in patients with HER2-low MBC.
Results: One hundred and seventy-nine patients were included: the majority with HR-negative tumours received SG first (ADC1) (n = 100/108) while most with HR-positive tumours received T-DXd first (n = 56/71). Median progression-free survival 2 was short: 2.7 months (95% CI: 2.4–3.3) in the whole population, respectively, 3.1 (95% CI: 2.6–3.6) and 2.2 months (95% CI: 1.9–2.7) for patients receiving T-DXd or SG second (ADC2). Intermediary lines of chemotherapy between ADC1 and ADC2 had no impact. Primary resistance to ADC2 occurred in 54.4% of patients. Certain patients showed initial response to ADC2.
Conclusions: Clinical benefit of sequentially administered SG and T-DXd is limited for most patients. Nevertheless, a subset of patients might benefit—on the short term—from a second ADC. Additional studies are needed to identify patients who could benefit from two ADCs with similar payloads.
British Journal of Cancer , résumé, 2024