213P Sequencing antibody-drug conjugates (ADCs) in patients (pts) with HER2-negative (HER2-) metastatic breast cancer (mBC)

ADCs are effective for pts with HER2- MBC but little is known about sequencing of different ADCs. We analyzed data from pts with HER2- MBC who received ≥2 ADCs and had ≥6 months (mo) follow-up at Dana-Farber Cancer Institute between 6/2014-1/2023. ADCs were grouped based on targets (HER2, Trop2, other) and payloads (topoisomerase inhibitor – TOPi; microtubule inhibitor - MI). We determined time to next treatment (tx) (TTNT) for ADC1, for the tx given immediately after ADC1 (postADC1), and for ADC2. TTNT-postADC1 was compared between pts who received consecutive ADCs or intervening tx between ADCs using an inverse probability weighting to account for non-randomized tx (adjustment for hormone receptor (HR)/HER2 IHC status at ADC1 start, year of ADC1 start, visceral disease at ADC1 start, TTNT-ADC1). We identified a total of 62 pts. Median age at MBC diagnosis was 51 (41-58) years. At ADC1 start, 29 pts (47%) had triple negative (TN) (17 HER2 low) and 33 (53%) pts had HR+ (21 HER2 low) MBC. A median of 1 (0-5) line of chemotherapy (CT) for MBC was given prior to ADC1 to both TN and HR+ MBC pts. Seven pts switched HER2 IHC status between ADC1 and ADC2 (3 from 0 to low, 4 from low to 0). Distribution of ADC1 was: 64% antiTrop2-TOPi, 23% antiHER2-TOPi, 13% nonHER2/nonTrop2-MI; for ADC2: 66% antiHER2-TOPi, 31% antiTrop2-TOPi, 3% nonHER2/nonTrop2-MI. The table reports TTNT for ADC1 and ADC2. A total of 26 pts had consecutive ADCs, while 36 pts had 1-5 intervening tx (median of 1 CT line, range 0-5) between ADCs. Median TTNT-postADC1 was 4.37 mo (95%CI 3.12-4.89) and did not differ if the postADC1 was another ADC or a different tx (HR 0.89, 95% CI 0.43-1.87, p=0.76). Genomic features and gene expression data from circulating tumor DNA (DNADX) will be presented.Table: 213PMedian TTNT for ADC1 and ADC2Median TTNT for ADC1Median TTNT for ADC2Overall population (n=62)4.34 mo (95% CI 3.68-5.52)5.39 mo (95% CI 3.91-8.38)HR+ MBC (n=33, 53%)4.66 mo (95% CI 3.09-5.75)5.62 mo (95% CI 3.91-NA)TNBC (n=29, 47%)4.11 mo (95% CI 3.68-6.87)5.29 mo (95% CI 2.66-NA)Median follow up: 23.1 mo Open table in a new tab In this cohort, most pts received antiTrop2 as ADC1 and antiHER2 as ADC2. Similar TTNT was observed with ADC1 and ADC2, irrespective of receptor status. Ongoing work is investigating biomarkers to guide tx sequencing.