Sacituzumab govitecan 180mg powder for solution for infusion vials

Sacituzumab govitecan (SG), a humanized antibody-drug conjugate, enables intra-tumor delivery of SN-38, the active metabolite of irinotecan, with the aim of increasing efficacy. SN-38 is predominantly inactivated by the polymorphically expressed uridine diphosphate glucuronosyltransferase 1A1 (UGT1AA) where reduced activity can lead to toxicity. SG toxicity closely resembles that of irinotecan. We conducted a systematic review and meta-analysis (PROSPERO ID: CRD42024598820) to assess UGT1A1 genotype as a determinant of SG toxicity. Studies published up to September 29, 2024, on UGT1A1 genotype and SG toxicity were eligible. Risk of bias was assessed using the STROPS guideline. Effect estimates for each genotype, comparing heterozygotes and homozygotes to wild-type, were analyzed. Odds ratios (ORs) with 95% Confidence Intervals (CIs) and forest plots were generated for each exposure-outcome combination. Four clinical trials including 999 UGT1A1 genotyped subjects were selected for the meta-analysis. SG treatment in UGT1A1*28 homozygous subjects increased the risk of toxicity. The OR (95% CI) was 1.80 (1.03-3.14) for neutropenia, 1.38 (0.90-2.10) for diarrhea, and 1.62 (1.07-2.45) for anemia of any grade, with low heterogeneity (I2 ≤ 28%). The OR for all severe (grade ≥ 3) toxicities combined was 7.03 (95% CI: 3.41-14.50, I2 = 18%). UGT1A*28 homozygous subjects were more likely to have dose reductions and treatment interruptions compared to wild-type individuals. In conclusion, individuals with UGT1A*28/*28 genotype are at an increased risk of severe SG-related toxicity. Pre-treatment genotyping should be used to identify individuals that may benefit from personalized dosing, closer monitoring or alternative therapies.

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Background/objectivesTriple-negative breast cancer is difficult to treat due to the absence of hormone receptors and Her2neu. Sacituzumab govitecan is a new therapeutic approach that uses an antibody directed against the Trop-2 antigen present in solid epithelial tumors, linked to the active metabolite SN-38, similar to irinotecan, to specifically target cancer cells while minimizing damage to healthy cells. The objective of the present review was to evaluate the efficacy and safety of sacituzumab govitecan as a single treatment in patients with triple-negative breast cancer and to compare its results with the standard conventional chemotherapy regimen currently used in this disease.MethodsA systematic review of randomized clinical trials of sacituzumab govitecan was performed. The search was performed in Medline (PubMed), Web of Science, and Cochrane from September 2022 to January 2024.ResultsThirty-eight articles are included and evaluated according to inclusion and exclusion criteria corresponding to the two most relevant clinical trials, including specific analyses of cohorts and subgroup study arms within these trials. Data from more recent clinical trials are also reviewed.ConclusionsThe efficacy results showed a significantly greater clinical benefit with sacituzumab govitecan compared to standard chemotherapy in patients with triple-negative breast cancer. This drug will become a treatment of substantial impact in future treatment guidelines for this type of cancer.

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BackgroundSacituzumab govitecan (SG) is an antibody-drug conjugate (ADC) that targets trophoblast cell-surface antigen 2 and is conjugated to SN-38, a potent topoisomerase I inhibitor. SG has demonstrated promising activity against various solid tumors. However, comprehensive evaluations of its efficacy and safety remain limited, and outcomes across studies have shown inconsistency. This systematic review and meta-analysis aimed to assess the therapeutic efficacy and associated adverse events (AEs) of SG in the treatment of solid tumors.MethodsA systematic search of PubMed, Embase, and the Cochrane Library was conducted to identify randomized controlled trials (RCTs) and single-arm studies published up to February 14, 2025. The primary outcomes included overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related AEs.ResultsFive RCTs comparing SG with chemotherapy were included in the analysis. SG significantly improved OS (risk ratio [RR] = 0.720; 95% confidence interval [CI]: 0.587-0.882; P = 0.002), PFS (RR = 0.682; 95% CI: 0.516-0.901; P = 0.007), and DCR (RR = 1.286; 95% CI: 1.034-1.599; P = 0.024). However, higher incidences of neutropenia, leukopenia, diarrhea, and anemia were observed in the SG group. In the single-arm meta-analysis, 16 cohorts from five trials were included. The pooled ORR was 21% (95% CI: 16%-27%), DCR was 62% (95% CI: 56%-69%), and the clinical benefit rate was 33% (95% CI: 26%-39%). The median pooled PFS, duration of response, and OS were 4.41 months (95% CI: 3.61-5.22 months), 7.40 months (95% CI: 5.99-8.82 months), and 10.29 months (95% CI: 7.75-12.83 months), respectively.ConclusionAlthough SG demonstrates superior OS, PFS, and DCR compared to chemotherapy in patients with solid tumors, this benefit is accompanied by an increased risk of specific adverse events. Subgroup analyses indicate that SG confers a more substantial clinical benefit in breast and urothelial cancers than in other tumor types.

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IntroductionSacituzumab govitecan (SG) as an antibody-drug conjugate targeting Trophoblast cell surface antigen 2, has emerged as a promising therapy for breast cancer. However, the efficacy of SG across disease subtypes, treatment settings, and in combination regimens remains incompletely defined.Materials and methodsA comprehensive literature search was conducted in PubMed, Embase, Web of Science, and the Cochrane Library to identify studies reporting the clinical efficacy and safety outcomes of SG in breast cancer. Pooled analyses were performed for overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (AEs). Subgroup analyses were performed by molecular subtype, disease stage, and treatment regimen.ResultsA total of 13 studies involving 2,447 patients with breast cancer were included. SG significantly improved ORR (OR = 3.97, 95%CIs: 1.32-11.90) and OS (HR = 0.59, 95%CIs: 0.47-0.75) versus single agent chemotherapy in RCTs, with pronounced benefit in metastatic triple-negative breast cancer (mTNBC) (ORR = 10.55; HR for OS: 0.50, 95%CIs: 0.43-0.58). Pooled median PFS (mPFS) was 4.95 months (95%CIs: 4.36-5.61months) in RCTs and 5.93 months (95%CIs: 4.76-7.39 months) in single-arm studies, with early-stage TNBC achieving mPFS up to 9.50 months (95%CIs: 8.91-10.13 months). Combination with immunotherapy suggested numerically longer survival (median OS 18.0 vs 12.2 months). The most frequent grade ≥3 AE was neutropenia, occurring in 26-57% of patients, with overall toxicity manageable and consistent across studies.ConclusionsSG provides substantial clinical benefit in breast cancer, improving ORR, OS, and PFS, particularly in TNBC, with consistent efficacy across monotherapy and combination regimens. The increased risk of hematologic and gastrointestinal toxicities warrants careful monitoring in clinical practice.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251072321.

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