Efficacy and safety of sacituzumab govitecan Trop-2-targeted antibody-drug conjugate in solid tumors and UGT1A1*28 polymorphism: a systematic review and meta-analysis.

Background: Sacituzumab govitecan (SG) is a promising Trop-2-targeted antibody-drug conjugate (ADC) approved for the treatment of metastatic triple-negative breast cancer (TNBC). Early phase clinical trials have demonstrated good clinical activity and safety profile of SG in various tumor types, albeit with differing response rates and durations. The aim of this systematic review and meta-analysis was to evaluate the clinical efficacy and toxicity of SG and the influence of UGT1A1*28 genotype in clinical trials involving solid tumors.

Methods: A systematic review of the literature from publicly available databases was performed on February 15, 2024 whereby studies published till 15 February 2024 were retrieved according to PRISMA guidelines [PROSPERO #CRD42022359943]. Data extracted included tumor type, sample size, demographic information, SG dose, UGT1A1*28 status, toxicity events, duration of follow-up, response, and survival outcomes. Risks of bias analysis was refereed using the Joanna Briggs Institute quality assessment tool for the cohort and RCT studies using 11 and 13 parameters, respectively. Statistical analysis was performed using the DerSimonian and Laird inverse variance methods. Heterogeneity was assessed using the I statistic and Χ tests. P value < 0.05 was considered as statistical significance.

Results: Eleven eligible clinical trials comprised of 1578 patients harboring various tumor types including TNBC, lung, genitourinary and gastrointestinal malignancies were included in the systematic review and meta-analysis. Pooled incidences of severe adverse events were minimal at <10%, with the exception of grade 3-4 neutropenia at 37.4%. The median PFS and OS across all studies were 4.9 (95%CI: 4.0-5.8) months and 9.6 (95%CI: 7.6-11.6) months, respectively. Objective response rate across all studies evaluated was 17.1% (95%CI: 12.0-22.1).

Conclusion: Our systematic review and meta-analysis confirmed that SG confers good clinical activity in certain solid tumor types and was tolerable with minimal adverse events. The potential utility of UGT1A1*28 genotyping in predicting clinical response and outcomes could not be determined due to the limited number of studies with available UGT1A1 genotype data.