Patients with breast cancer treated with trastuzumab deruxtecan and/or sacituzumab govitecan in the real-world: preliminary outcome data

Keywords

real-world data - Trastuzumab Deruxtecan - Sacituzumab Govitecan

Introduction: Novel antibody-drug conjugates (ADCs) have been recently approved in metastatic breast cancer. Trastuzumab deruxtecan (T-DXd) in HER2+ or HER2 low disease, while Sacituzumab Govitecan (SG) in triple negative breast cancer (TNBC) or hormone receptor (HR) +/HER2- disease. Given their high cost and risk of serious adverse events, early monitoring of their real-world adoption and outcomes is critical.

Objective: To determine clinicopathological characteristics of breast cancer patients exposed to T-DXd and SG, either alone or sequentially, and estimate Time to Treatment Discontinuation (TTD) as a surrogate of progression or intolerable toxicity events.

Methods: retrospective observational study from all breast cancer patients with T-DXd and SG prescriptions in a private healthcare outpatient network of clinics. Data were extracted from the Oncoclínicas Electronic Health Records database using technology-based abstraction and human curation by experts. Descriptive analysis was performed for variables such as age, molecular subtype, treatment line, and TTD was calculated using the Kaplan-Meier method.

Results: In total, 383 patients were included. Median age was 57 years. T-DXd was administered in 255 cases (67%), SG in 105 (27%) and both ADCs in 23 patients (6%). There was more than two-fold increase in ADC use in 2023 (n = 280) as compared to 2022 (n = 103). For T-DXd, 54% were HER2+, 32% HER2-low/TNBC and 14% HER2-low/HR+. For SG, 82% were TNBC and 18% HR+/HER2-. Most patients used ADCs from the third line or beyond, representing 57% for T-DXd and 62% for SG. With a median follow-up of 8 months, 45 death events were reported (12%). Median TTD was 8 months (95% CI 6.78 - 8.63) for T-DXd and 4 months (95% CI 3.21 - 4.30) for SG. In the population that used both ADCs, most patients (61%) received T-DXd followed by SG. Median TTD of the first and second ADC treatments were 6 months (95% CI 3.83 - 8.86) and 3 months (95% CI 1.40 – 3.80), respectively.

Conclusion: There was a significant increase in novel ADC use for breast cancer in recent years. Clinicopathological features of patients treated in the real-world are comparable to clinical trials, but most cases were heavily pre-treated when starting T-DXd or SG, potentially reducing their effectiveness. Longer follow-up and stratified analysis by molecular subtype will shed more light on the outcomes when compared to clinical trials.

Corresponding author: Christopher Lucas Negrete (e-mail: [e-mail]).