Abstract P3-07-08: Exposure-adjusted incidence rates (EAIRs) of adverse events (AEs) from the phase 3 TROPiCS-02 study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in HR+/HER2- metastatic breast cancer (MBC)

Abstract Background: SG is a Trop-2-directed antibody-drug conjugate approved by the FDA for patients (pts) with metastatic triple-negative breast cancer who received ≥2 prior chemotherapies (≥1 for MBC). In the phase 3 TROPiCS-02 study, SG demonstrated a 34% reduction in risk of progression or death vs TPC in heavily pretreated, endocrine-resistant HR+/HER2– MBC (Rugo H, et al. ASCO 2022. LBA1001). The safety profile was manageable, with neutropenia and diarrhea as the key AEs. Absolute incidence rate is the most used metric to summarize AEs in routine clinical safety analyses. However, when the treatment duration differs significantly between treatment arms, these rates may need adjustment to account for longer treatment exposure, which may incur a higher incidence of AEs. Given that the median treatment duration was longer for SG in TROPiCS-02, EAIRs were assessed in post hoc safety analyses. Methods: Pts with HR+/HER2– unresectable locally advanced or MBC and 2-4 prior chemotherapy regimens for MBC were randomized 1:1 to receive SG or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until unacceptable toxicity or disease progression. The primary endpoint was progression-free survival per RECIST 1.1 by central review. Safety was a secondary endpoint. Time-at-risk EAIR considers pts’ exposure of a specific AE in quantifying the risk of AE, defined as the number of pts who experienced at least 1 specific AE, divided by the total exposure time (pt-year of exposure [PYE]) in each arm. For pts who experienced specific AEs, exposure time was calculated from first dose date up to the first AE onset, and for pts who did not, from first dose up to data cutoff (if still on study treatment) or up to last dose (if discontinued study treatment). The 95% CI of the EAIR difference is a standard method to assess the statistical significance of AE incidence rate differences between arms. Results: Of 543 pts enrolled (median age, 56 y; visceral metastases, 95%; prior CDK4/6 inhibitor for MBC, 99%; median lines of chemotherapy for MBC, 3), 517 pts (SG, n=268; TPC, n=249) received ≥1 dose of study treatment. At data cutoff (Jan 3, 2022), 18 pts (7%) vs 4 pts (2%) remained on treatment in the SG vs TPC arms; median treatment duration was 4.1 months and 2.3 months, respectively. The absolute incidence, EAIRs (incidence per 1 PYE), and EAIR differences for the overall safety summary and most common grade ≥3 TEAEs are provided (Table). Overall, SG had higher absolute incidence rates vs TPC for grade ≥3 treatment-emergent AEs (TEAEs), serious AEs, and TEAEs leading to death, but the EAIRs were similar between arms, suggesting an association with duration of treatment exposure. When adjusted for exposure, the incidence of grade ≥3 diarrhea remained higher for SG vs TPC; however, the incidence of grade ≥3 neutropenia was similar between arms. Conclusions: The safety profile of SG was manageable in pts with heavily pretreated HR+/HER2– endocrine-resistant, unresectable locally advanced or MBC. Though there was a higher absolute incidence of TEAEs leading to death and grade ≥3 neutropenia with SG vs TPC, the EAIRs were similar. Taken together with the efficacy benefit with SG, this supports a favorable risk/benefit profile for SG compared with standard chemotherapy in this pt population with limited therapeutic options. Table. Overall Safety Summary and Summary of Common (Absolute Incidence ≥5%) Grade ≥3 TEAEs With Absolute Incidence, Exposure-Adjusted Incidence Rates (EAIRs),a and EAIR Differencesb,c Citation Format: Sara Tolaney, Peter Schmid, Aditya Bardia, Frederik Marmé, Delphine Loirat, Priyanka Sharma, Hao Wang, Olivia Fu, Wendy Verret, Hope Rugo. Exposure-adjusted incidence rates (EAIRs) of adverse events (AEs) from the phase 3 TROPiCS-02 study of sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) in HR+/HER2- metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-07-08.