Sequential use of antibody-drug conjugate after antibody-drug conjugate for patients with metastatic breast cancer: ADC after ADC (A3) study.

• DOI: 10.1200/jco.2023.41.16_suppl.1022
• Publication Date: 2023-06-04T14:10:33Z
• Authors: Rachel Occhiogros...; Laura Spring; Geoffrey G. Fell; Phoebe Ryan; Neelima Vidula; Arielle J Medford; Jennifer Shin; Elizabeth Abraham; Seth Andrew Wander; Steven J. Isakoff; Beverly Moy; Leif W. Ellisen; Aditya Bardia
• Keywords: Antibody-drug conjugate

1022 Background: Optimizing sequential use of Antibody Drug Conjugates (ADCs) is an area unmet need and rising clinical importance. With the recent approvals sacituzumab govitecan (SG) for HR+/HER2- triple negative metastatic breast cancer (MBC) as well trastuzumab deruxtecan (T-DXd) HER2-low MBC, many patients are now candidates multiple ADCs. However, given potential cross-resistance based on antibody target vs payload (Coates et al, Cancer Discov. 2021), optimal sequencing remains uncertain. We evaluated safety efficacy ADC after with HER2 MBC. Methods: included all at academic institution treated more than one Each line beyond first was presence same “antibody target” or “payload” compared to prior ADC. Clinicopathological information gathered by chart review. defined “cross-resistance” progressive disease (PD) time restaging second Progression-free survival (PFS) from start treatment progression death any cause. All PFS estimation done using KM method. pairwise comparisons across were a Wilcoxon Rank Sum test allow divergences normality in times. Significance declared type I error less 0.05. Results: A total 193 MBC ADCs between August 2014-February 2023. Among these,32 identified having received (HR+/HER2- = 13, TNBC 19, low 22). Median age 57.1 years (range 31.3-88.6) had median 4 lines 2-12) before initiation The used (ADC1) significantly longer 7.55 months (95% CI 3.22-10.25) 2.53 (ADC2) 1.38-4.14) (p=0.006). ADC2 change 3.25 1.38 months, n/a) 2.30 no (p=0.16). At imaging, present 17 cases (53.1%), absent 12 (37.5%), not evaluable 3 cases. When contained first, 9/13 (69.2%), 8/16 (50.0%) when targeted different tumor antigen. Similarly, differences noted switch not. Conclusions: This study highlights subset that ADC, while others durable responses latter therapy, particularly if utilized. Further research needed validate these findings discern mechanisms resistance guide ADC-based options.