medwireNews: Further findings from the TROPHY-U-01 trial indicate that the Trop-2-directed antibody–drug conjugate sacituzumab govitecan (SG) has efficacy in heavily pretreated patients with metastatic urothelial cancer (mUC).
The initial findings for the phase 2 study were reported at the ESMO Congress in 2019 and updated results have now been presented at the ESMO Virtual Congress 2020 by Yohann Loriot, from Institut Gustave Roussy in Villejuif, France.
Yohann Loriot discusses the TROPHY-U-01 trial update (5:26)
“The final results of the TROPHY-U-01 cohort 1 confirm the interim findings and prior phase 1/2 study results and demonstrate that SG is generally well tolerated and has significant anticancer activity in heavily pretreated mUC patients who progressed on both platinum-based chemotherapy and checkpoint inhibitors,” the presenter said.
Noting that SG has received US FDA fast-track designation in this patient population, he suggested that it “may have the potential to change practice in this setting.”
Overall, 113 patients were given SG 10 mg/kg on days 1 and 8 of a 21-day cycle, with treatment continuing in 14% of the group at time of data analysis in May 2020.
After a median 6.3 months of follow-up, the objective response rate (ORR) was 27%, including a 5% complete response rate, which exceeded the required target of 12% to meet the study’s primary endpoint, Loriot explained.
Patients continued treatment for a median 3.7 months and a maximum of 16.0 months, with a median duration of response of 5.9 months.
This resulted in median progression-free survival (PFS) and overall survival (OS) of 5.4 and 10.5 months, respectively, although Loriot suggested the latter figure may “underestimate” the true OS in the study as SG treatment is ongoing in eight of the 31 responding patients.
Regardless, he believes that the ORR and survival results “compare favorably” with those for studies of single-agent chemotherapy, citing an ORR of around 10%, and PFS and OS rates of 2–3 and 7–8 months, respectively.
Safety analysis indicated that diarrhea (65%), nausea (58%), fatigue (50%), and alopecia (47%) were the most common treatment-related adverse events associated with SG, with the majority of events occurring at grade 3 or below.
In addition, almost half (46%) of SG-treated patients developed neutropenia and 10% febrile neutropenia. Loriot said that this side effect was reversible and manageable with dose delays or reduction, and granulocyte colony-stimulating factor treatment, although three patients discontinued therapy because of neutropenia and one patient died from sepsis related to febrile neutropenia.
The presenter concluded that a phase 3 confirmatory trial – TROPiCS-04 – is currently underway to assess the use of SG versus a physician’s choice of docetaxel, paclitaxel, or vinflunine chemotherapy. The trial is recruiting patients with unresectable locally advanced or mUC who have progressed after platinum-based chemotherapy and PD-1 or PD-L1 inhibitors, or patients who have early progression after neoadjuvant platinum chemotherapy and checkpoint inhibitor therapy.
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This independent news story was supported by an educational grant from Pfizer and Merck Healthcare KGaA, Darmstadt, Germany