Sacituzumab govitecan in advanced urothelial carcinoma: TROPiCS-04, a phase III randomized trial.

We report the results from final analysis of the global open-label randomized phase III TROPiCS-04 study (NCT04527991) in pretreated aUC.

我们报告了全球开放标签随机III期TROPiCS-04研究（NCT04527991）在既往治疗的aUC中的最终分析结果。

patients_and_methods

Patients with aUC whose disease had progressed on prior platinum-based chemotherapy and checkpoint inhibitor therapy were randomized 1 : 1 to receive SG or treatment of physician's choice (TPC; paclitaxel, docetaxel, or vinflunine).

先前接受过基于铂的化疗和检查点抑制剂治疗且疾病进展的aUC患者被随机1:1分配接受SG或医生选择的治疗（TPC；紫杉醇、多西他赛或长春瑞滨）。

The primary endpoint was overall survival(OS).

主要终点是总生存（OS）。

Secondary endpoints included progression-free survival(PFS) and objective response rate(ORR) by investigator and blinded independent committee review, as well as safety.

次要终点包括通过研究者和盲审独立委员会评审的无进展生存期（PFS）和客观缓解率（ORR），以及安全性。

Results

Overall, 711 patients were randomized.

总体而言，共有711名患者被随机分配。

After a median follow-up of 9.2 months, the primary endpoint was not met [median OS for SG versus TPC: 10.3 months versus 9.0 months, hazard ratio(HR) 0.86, 95% confidence interval(CI) 0.73-1.02, P = 0.087].

经过中位随访9.2个月后，主要终点未达到[SG组与TPC组的中位总生存期分别为10.3个月和9.0个月，风险比（HR）为0.86，95%置信区间（CI）为0.73-1.02，P = 0.087].

Median PFS with SG and TPC was 4.2 months and 3.6 months, respectively (HR 0.86, 95% CI 0.72-1.03); ORR (95% CI) was 23% (18% to 27%) and 14% (10% to 18%).

SG组和TPC组的中位无进展生存期分别为4.2个月和3.6个月（HR 0.86，95% CI 0.72-1.03）；客观缓解率（ORR，95% CI）分别为23%（18%至27%）和14%（10%至18%）。

The most common grade ≥3 treatment-related adverse event(TRAE) with SG was neutropenia (35%, including 12% with febrile neutropenia).

使用SG治疗时，最常见的3级或以上治疗相关不良事件（TRAE）是中性粒细胞减少症（占35%，其中12%伴有发热性中性粒细胞减少症）。

Incidenceof grade ≥3 TRAEs (67% versus 35%) and grade 5 treatment-emergent adverse events (TEAEs; 7% versus 2%) was higher with SG versus TPC.

与TPC相比，使用SG治疗时3级或以上TRAE的发生率（67%对比35%）以及5级治疗后不良事件（TEAEs；7%对比2%）更高。

In the SG group, 16/25 grade 5 TEAEs were infections with neutropenia mostly occurring early in the treatment course of patients with multiple risk factors for febrile neutropenia.

在SG组中，25例5级严重不良事件中，有16例是感染，其中以中性粒细胞减少症为主，这主要发生在有发热性中性粒细胞减少症多种风险因素的患者治疗早期。

Primary prophylactic granulocyte colony-stimulating factor (G-CSF) usage with SG and TPC was 21% and 22%, respectively.

SG和TPC的原发性预防性粒细胞集落刺激因子（G-CSF）使用率分别为21%和22%。

Conclusions

SG did not result in a significant improvement in OS or PFS compared with TPC in pretreated aUC, although SG activity was demonstrated by a higher ORR.

SG 与 TPC 相比，在预处理的 aUC 中并未显著改善总生存期（OS）或无进展生存期（PFS），尽管通过更高的客观缓解率（ORR）显示了 SG 的活性。

Early toxicity-related complications with SG may have impacted efficacy outcomes.

SG 的早期与毒性相关的并发症可能影响了疗效结果。