Safety profile of sacituzumab govitecan in patients with breast cancer: A systematic review and meta-analysis.

e13106 Background: Sacituzumab govitecan (SG), a first-in-class TROP-2-directed antibody conjugated to a topoisomerase inhibitor, has shown antitumor activity across various breast cancer (BC) subtypes. Following SG approval for metastatic triple negative breast cancer (TNBC) and its broad use, understanding SG’ safety profile is crucial. Hence, we conducted a systematic review and meta-analysis to evaluate the safety and tolerability of SG in patients with BC. Methods: We comprehensively searched PubMed, Embase, and Cochrane databases, and ASCO and ESMO websites for clinical trials assessing the safety of SG in BC patients. Outcomes of interest included treatment-related adverse events (TRAEs) of any grade, grade 3/4, adverse events (AEs) leading to death, and AEs leading to SG dose reduction or discontinuation. All analyses were performed in R software (v.4.2.2) using random effects models. Heterogeneity was assessed using I 2 test. Results: A total of 1,325 patients from six studies – three randomized clinical trials (RCTs) and three non-RCTs – were included. Median age of population ranged from 47 to 56 years. Most had metastatic disease (86%, n=1187), and triple-negative BC (48.6%, n=670). Regarding therapies, 798 patients received SG and 527 had treatment of physician's choice (TPC). In the pooled analysis of 748 patients on SG, the overall risk of AEs was 100% (95% CI 99-100%). The estimated risk of the most common all grade AEs were neutropenia (66%), anemia (44%), nausea (56%), vomiting (30%), fatigue (46%), constipation (17%), diarrhea (45%), and alopecia (46%), as described (Table). The risk of grade 3/4 AEs among 748 patients on SG was 55% (95% CI 36-74%). Neutropenia was the most important grade ≥3 AE, with a estimated frequency of 47%; followed by anemia and diarrhea, with an incidence of at 9% and 7%, respectively. The incidence of all other grade 3/4 AEs (e.g. anemia, vomiting, leukopenia, fatigue, constipation, and diarrhea) was below 10%. Dose reduction and discontinuation were observed in 14.4% and 2.9% of patients, respectively. Toxicity-related deaths occurred in six patients (0.4%). In a comparative sensitivity analysis of RCTs only, SG had significantly higher toxicity than TCPs, all grade AEs (OR 12.30 95%CI 1.68-89.87, p=0.01), and grade >3 AEs (OR 1.69 95%CI 1.25-2.28, p=0.0006). Conclusions: In this systematic review and meta-analysis, SG was associated with a high incidence of AEs. Neutropenia is a notable and potentially serious adverse event. Toxicity associated with SG may be addressed through close monitoring and early management. [Table: see text]