1. The objective response rate was 28% with a complete response of 5.6% and a partial response of 23%.
2. Treatment-related adverse events grade ≥3 occurred in 65%, most commonly included neutropenia, leukopenia, and anemia.
Evidence Rating Level: 2 (Good)
Study Rundown: Treatment of advanced urothelial carcinoma remains challenging, with traditional chemotherapy showing limited efficacy. A recent trial has shown that sacituzumab govitecan (SG), an antibody-drug conjugate, had some positive outcome measures in metastatic urothelial carcinoma after the progression of chemotherapy and immunotherapy. This study provides an update to the previous study with a longer follow-up period. The primary endpoint was objective response rate (ORR), and secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. This study also investigated mutations in the UGT1A1 gene, particularly UGT1A128, as it reduces the metabolism of SG and those may face an increased risk of adverse events. ORR was found to be 28%, with complete response seen in 5.3% and partial response in 23%. Clinical benefit ratio was found to be 38%. Median DoR was 8.2 months. Median PFS was 5.4 months, and PFS at 12 months was 14%. Median OS was 10.9 months and OS at 12 months was 45%. With regards to safety, treatment related adverse events grade ≥3 occurred in 65%, most commonly included neutropenia (35%), leukopenia (18%), anemia (14%). UGT1A1 status was found to be 40% homozygous wildtype UGT1A1 allele, 42% heterozygous for the UGT1A128 allele, and 12% homozygous for the UGT1A128 allele. Treatment related adverse events grade ≥3 occurred in 79% of those homozygous for the UGT1A128 allele compared to 62% of those homozygous for wildtype. The strengths of this study include increased follow-up time and UGT1A1 gene testing, and the limitations include small sample size. Overall, this study found favorable outcome measures in patients with resistant advanced urothelial carcinoma who were treated with SC.
Click to read the study in Ann. Oncol.
In-Depth [prospective cohort]: This international, open-label, phase II study enrolled patients with unresectable locally advanced or metastatic urothelial carcinoma who progressed after platinum-based chemotherapy and immunotherapy, and started them on SG (113 patients). Median follow-up was 10.5 months (range, 0.3-40.9). ORR was found to be 28% (95%CI 20.2-37.6), with complete response seen in 5.3% and partial response in 23.0%. Clinical benefit ratio was found to be 38% (95%CI 29.1-47.7). Median DoR was 8.2 months (95%CI 4.7-13.7). Median PFS was 5.4 months (95%CI 3.5-6.9), and PFS at 12 months was 14% (95%CI 7.2-23.3). Median OS was 10.9 months (95%CI 8.9-13.8) and OS at 12 months was 45% (95%CI 35.4-53.8). With regards to safety, treatment related adverse events grade ≥3 occurred in 65%, most commonly included neutropenia (35%), leukopenia (18%), anemia (14%). UGT1A1 status was found to be 40% homozygous wildtype UGT1A1 allele, 42% heterozygous for the UGT1A128 allele, and 12% homozygous for the UGT1A128 allele. Treatment related adverse events grade ≥3 occurred in 79% of those homozygous for the UGT1A128 allele compared to 62% of those homozygous for wildtype. Overall, this study found favorable outcome measures in patients with resistant advanced urothelial carcinoma who were treated with SC.
Image: PD
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