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 ( I 2 ≤ 28%). The OR for all severe (grade ≥ 3) toxicities combined was 7.03 (95% CI: 3.41–14.50, I 2 = 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: Sacituzumab 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. Methods: A 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. Results: Five 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. Conclusion: Although 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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Sacituzumab govitecan (SG) significantly improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in hormone receptor-positive human epidermal growth factor receptor 2-negative (HR+HER2−) metastatic breast cancer (mBC) in the global TROPiCS-02 study. TROPiCS-02 enrolled few Asian patients. Here we report results of SG in Asian patients with HR+HER2− mBC from the EVER-132-002 study. Patients were randomized to SG (n = 166) or chemotherapy (n = 165). The primary endpoint was met: PFS was improved with SG versus chemotherapy (hazard ratio of 0.67, 95% confidence interval 0.52–0.87; P = 0.0028; median 4.3 versus 4.2 months). OS also improved with SG versus chemotherapy (hazard ratio of 0.64, 95% confidence interval 0.47–0.88; P = 0.0061; median 21.0 versus 15.3 months). The most common grade ≥3 treatment-emergent adverse events were neutropenia, leukopenia and anemia. SG demonstrated significant and clinically meaningful improvement in PFS and OS versus chemotherapy, with a manageable safety profile consistent with prior studies. SG represents a promising treatment option for Asian patients with HR+HER2− mBC (ClinicalTrials.gov identifier no. NCT04639986 ). In the phase 3 EVER-132-002 trial, patients with HR+HER2− metastatic breast cancer from Asia were treated with the Trop-2-directed antibody–drug conjugate sacituzumab govitecan or chemotherapy, and those receiving sacituzumab govitecan experienced prolonged progression-free survival compared with patients treated with chemotherapy.

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PURPOSE The open-label, phase III EVOKE-01 study evaluated sacituzumab govitecan (SG) versus standard-of-care docetaxel in metastatic non–small cell lung cancer (mNSCLC) with progression on/after platinum-based chemotherapy, anti–PD-(L)1, and targeted treatment for actionable genomic alterations (AGAs). Primary analysis is reported. METHODS Patients were randomly assigned 1:1 (stratified by histology, best response to last anti–PD-(L)1–containing regimen, and AGA treatment received or not) to SG (one 10 mg/kg intravenous infusion on days 1 and 8) or docetaxel (one 75 mg/m 2 intravenous infusion on day 1) in 21-day cycles. Primary end point was overall survival (OS). Key secondary end points were investigator-assessed progression-free survival (PFS), objective response rate, patient-reported symptom assessment, and safety. RESULTS In the intention-to-treat population (SG, n = 299; docetaxel, n = 304), 55.4% had one previous line of therapy. Median follow-up was 12.7 months (range, 6.0-24.0). The primary end point was not met. There was a numerical OS improvement for SG versus docetaxel (median, 11.1 v 9.8 months; hazard ratio [HR], 0.84 [95% CI, 0.68 to 1.04]; one-sided P = .0534), consistent across squamous and nonsquamous histologies. Median PFS was 4.1 versus 3.9 months (HR, 0.92 [95% CI, 0.77 to 1.11]). An OS benefit was observed for SG (n = 192) versus docetaxel (n = 191) in mNSCLC nonresponsive to last anti–PD-(L)1–containing regimen (3.5-month median OS increase; HR, 0.75 [95% CI, 0.58 to 0.97]); this was consistent across histologies. Among patients receiving SG and docetaxel, 6.8% and 14.2% discontinued because of treatment-related adverse events (TRAEs), respectively; 1.4% and 1.0%, respectively, had TRAEs leading to death. CONCLUSION Although statistical significance was not met, OS numerically improved with SG versus docetaxel, which was consistent across histologies. Clinically meaningful improvement in OS was noted in mNSCLC nonresponsive to last anti–PD-(L)1–containing regimen. SG was better tolerated than docetaxel and consistent with its known safety profile, with no new safety signals.

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Objective: The objective of this multicenter, observational, retrospective analysis was to evaluate the safety and efficacy of sacituzumab govitecan in metastatic triple-negative breast cancer (mTNBC) patients managed according to common clinical practice in Italy. Methods: Data were retrieved by 7 sites. Triple-negative BC was defined by the lack of expression of estrogen receptor (ER <1%), progesterone receptor (PgR <1%) and human-epidermal growth factor receptor-2 (HER2 0, 1+, 2+ ISH-not amplified) according to standard ASCO-CAP criteria. Demographic and clinical characteristics were collected. Premedication, dose modifications and treatment schedule were based on the approved label of the product. Adverse events (AEs) were assessed according to NCI-CTCAE v5.0. Results: Fifty-seven eligible patients who received sacituzumab govitecan for mTNBC were included. Median age was 53 years (range 25-75). Approximately 70% of patients had an initial diagnosis of TNBC. Median time from the diagnosis of metastatic BC to start of sacituzumab govitecan was 17 months (range 0-97) and median number of previous therapies was 3 (range 1-7). The most common sites of metastasis were lymph nodes (63.1% of patients), lung (57.9%), bone (50.8%) and liver (38.6%). Eight (14.0%) patients had a disease-free interval ≤12 months. A total of 32 (56.1%) deaths were observed and the median overall survival (OS) was 12.43 months (95% CI, 7.97 months-not reached). At a median follow-up of 10.6 months, 45 patients (78.9%) had progression and the median progression-free survival (PFS) was 4.9 months (95% CI, 3.7-7.1 months). Partial tumour response was observed in 19 patients (33.3%), stable disease in 16 (28.1%) and disease progression in 22 patients (38.6%). The most common treatment-related AEs were anemia (66.6% of patients), alopecia (66.6%), neutropenia (59.6%), nausea (42.1%) and diarrhea (38.6%). Neutropenia was the most common serious treatment-related AE: 21.0% and 8.7% of patients experienced grade 3 or 4 neutropenia, respectively. Twenty-two patients (38.6%) reduced the dose and 5.3% permanently discontinued treatment. Conclusion: The results of this real-world analysis showed that both safety and efficacy of sacituzumab govitecan in mTNBC patients are consistent with that previously reported in regulatory trials. The use of premedication and supportive measures was associated with a satisfactory toxicity profile.

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