Multicenter retrospective cohort study of the sequential use of the antibody-drug conjugates (ADCs) trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) in patients with HER2-low metastatic breast cancer (MBC): Updated data and subgroup analyses by age, sites of disease, and use of intervening therapies.

Laura Ann Huppert University of California, San Francisco, San Francisco, CA info_outline Laura Ann Huppert, Reshma L. Mahtani, Samantha Catherine Fisch, Naomi Dempsey, Sarah Premji, Angelina Taylor, Saya Jacob, Laura Quintal, Michelle E. Melisko, Amy Jo Chien, Ana Cristina Sandoval-Leon, Lauren Carcas, Manmeet Singh Ahluwalia, Natasha Harpalani, Jenna Hoppenworth, Dame Idossa, Ruta D. Rao, Karthik Giridhar, Hope S. Rugo

Authors Laura Ann Huppert University of California, San Francisco, San Francisco, CA info_outline Laura Ann Huppert, Reshma L. Mahtani, Samantha Catherine Fisch, Naomi Dempsey, Sarah Premji, Angelina Taylor, Saya Jacob, Laura Quintal, Michelle E. Melisko, Amy Jo Chien, Ana Cristina Sandoval-Leon, Lauren Carcas, Manmeet Singh Ahluwalia, Natasha Harpalani, Jenna Hoppenworth, Dame Idossa, Ruta D. Rao, Karthik Giridhar, Hope S. Rugo Organizations University of California, San Francisco, San Francisco, CA, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, Mayo Clinic, Rochester, MN, Rush University Medical Center, Chicago, IL, Department of Clinical Pharmacy, University of California, San Francisco, San Francisco, CA, Charles E. Schmidt College of Medicine at Florida Atlantic University, Fort Lauderdale, FL, University of Minnesota, Minneapolis, MN, University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA Abstract Disclosures Research Funding No funding sources reported Background: T-DXd and SG are both FDA-approved treatments for patients (pts) with HER2-low MBC, but little data exists on the sequential use of these ADCs. Methods: In this multicenter retrospective cohort study, we identified pts with HER2-low MBC treated sequentially with both T-DXd and SG in either order, with or without intervening therapies (IntTx), at 5 academic centers between 2020-2023. We previously reported real-world progression free survival (rwPFS) and real-world overall survival (rwOS) by HR-status and ADC sequence order. Here we provide updated rwPFS and rwOS data, as well as new subgroup analyses by age, sites of disease, and use of IntTx between ADCs for HR- and HR+ disease. Results: 84 pts with HER2-low MBC treated with both T-DXd and SG were included, including 56 pts with HR+/HER2-low MBC (66.7%) and 28 pts with HR-/HER2-low MBC (33.3%). Prior to the start of ADC1, median age was 58 yrs and 22 pts were >65 yrs (26.2%), 65 pts (77.4%) had visceral disease, and 14 pts (16.7%) had central nervous system (CNS) disease. 36 pts (42.9%) had an IntTx between ADCs. Table 1 shows updated rwPFS and rwOS data by HR-status and ADC sequence order. For pts with HR+ and HR- MBC, there was no difference in ADC1 rwPFS or ADC2 rwPFS by age ≤65 vs. >65 yr or by presence vs. absence of visceral disease. For pts with HR- MBC, ADC1 rwPFS and rwOS was shorter for pts with CNS disease vs. pts without CNS disease (rwPFS 5.4 mo (n=6) vs. 8.5 mo (n=22), p=0.03; rwOS 11.6 mo vs. 21.1 mo, p<0.01 respectively). For pts with HR+ and HR- MBC, there was no difference in ADC2 rwPFS with or without receipt of IntTx. There was no difference in time to treatment failure for first IntTx vs. ADC2 if no InTx was given. Conclusions: This is one of the largest multicenter cohorts of pts treated with sequential ADCs for HER2-low MBC. Median rwPFS was longer for ADC1 than ADC2 in all subgroups, regardless of HR-status, ADC sequence order, age ≤65 or >65 yr, presence of visceral disease, or use of IntTx. Among pts with HR-/HER2-low MBC, pts with CNS disease had shorter ADC1 rwPFS and rwOS than pts without CNS disease. rwPFS and rwOS by HR-status and ADC sequence order*. HR+/HER2-low MBC (n=56) HR-/HER2-low MBC (n=28) SG → TDXd, n (%) 24 (42.9%) 25 (89.3%) Median lines tx for MBC prior to ADC1, range 3 (0-9) 2 (0-5) Median rwPFS ADC1, mo 8.0 7.8 Median rwPFS ADC2, mo 3.7 2.8 Median rwOS ADC1, mo 22.8 16.5 Median rwOS ADC2, mo 7.8 6.5 TDXd → SG, n (%) 32 (57.1%) 3 (10.7%) Median lines tx for MBC prior to ADC1, range 4.5 (2-10) 3 (1-5) Median rwPFS ADC1, mo 5.5 Not evaluable Median rwPFS ADC2, mo 2.6 Median rwOS ADC1, mo 17.7 Median rwOS ADC2, mo 5.8 *Data cutoff 01/10/24. Most pts were off ADC2 at last data cutoff.