Abstract P1-02-02: Indirect comparison of sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) in advanced breast cancer (aBC): safety and efficacy analysis

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Abstract Background: SG and Dato-DXd are antibody drug conjugates (ADCs) used in aBC. Both target humanized anti-trophoblast cell-surface antigen 2 (TROP2) and both have a similar (irinotecan-based) payload. There are few comparative data on these drugs. Methods: We searched MEDLINE, as well as proceedings from ASCO, ESMO and SABCS. Eligible studies were trials (dose expansion phase 1, phase 2 or 3) that evaluated Dato-DXd or SG in aBC patients. Safety (adverse effects [AE]) data were pooled as the mean, weighted by individual study sample size and indirect comparisons were performed using the test of two proportions (z score). For randomized trials of ADCs compared to chemotherapy, we performed a network metanalysis (using WINBUGS within Microsoft Excel) and report the hazard ratio (HR) for efficacy (overall survival [OS], progression free survival [PFS]) and odds ratio (OR) for AEs comparing Dato-DXd to SG. Statistical significance was defined as p<0.05. Results: Nine studies were included in the analysis, 3 for Dato-DXd and 6 for SG. A total of 450 patients were treated with Dato-DXd and 831 with SG. Median prior lines of treatment were 1 (range 1-6) for Dato-DXd and 4 (range 0-7) for SG. There were no significant differences in discontinuation due to toxicity (OR 0.97; 95% confidence interval [CI] 0.38-2.48)) or in toxic deaths (OR 1.11; 95% CI 0.15-8.34). Similarly, there were no significant differences in PFS (HR 0.95; 95% CI 0.71-1.28) or in OS (HR 1.06; 95% CI 0.74-1.53). Comparison of individual AEs between Dato-DXd and SG demonstrated the following: all grade AE (94.8% vs 100%, p < 0.01), grade≥ 3 AE (20.7% vs 75%, p< 0.01) and dose reduction (19.5% vs 26%, p=0.01). Ocular AE(all grade, 25.2%; grade ≥3, 1%), infusion reaction (all grade, 11.8%) and interstitial lung disease (ILD, all grade, 2.6%; grade ≥3 1%) were reported only with Dato-DXd, whereas febrile neutropenia (5.6%) and neuropathy (all grade, 11.8%; grade ≥3, 0.7%) were reported only with SG. SG showed more frequent hematological toxicities: anemia (grade ≥3, 1.7% vs 19%, p<0.01), neutropenia (grade ≥3, 1% vs 49%, p<0.01) and thrombocytopenia (grade ≥3, 0% vs 1.6%). SG was associated with more diarrhea (16.5% vs 58%, p<0.01, grade ≥3[SG only], 9.2%) while stomatitis was seen more with Dato-DXd (60.1% vs 11.9%, p<0.01; grade ≥3, 6.9% vs 1.4%, p<0.01). Alopecia (36% vs 45.6%, p<0.01) and fatigue (27% vs 46.7%, p<0.01; grade ≥3, 2.5% vs 5%, p=0.03) were more common with SG. Risk of grade 3 nausea and vomiting, as well as skin related AEs and dyspnea were similar. Conclusions: Both Dato-DXd and SG have similar risk of discontinuation without progression and toxic death. The side effect profile of SG is driven by hematological toxicities. AEs such as ILD, ocular and infusion reactions appear unique to Dato-DXd. Febrile neutropenia, neuropathy and fatigue were observed predominantly with SG. Among GI AEs, stomatitis is prominent for Dato-DXd and diarrhea with SG. There does not appear to be any meaningful difference in efficacy. These results may inform choice of therapy in clinical practice. Citation Format: Neha Pathak, Sudhir Kumar, Yael Berner-Wygoda, Abhenil Mittal, Diego Malon, Massimo Di Iorio, Jacqueline Savill, Consolacion Molto Valiente, Meredith Li, Michelle Nadler, Eitan Amir. Indirect comparison of sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) in advanced breast cancer (aBC): safety and efficacy analysis [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-02-02.

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