Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: Final analysis of cohort 1 participants of the TROPHY-U-01 trial suggests that sacituzumab govitecan (SG) may be a feasible option for patients with metastatic urothelial carcinoma (mUC) who have previously progressed on platinum chemotherapy and checkpoint inhibitors.
Yohann Loriot, from Institut Gustave Roussy in Villejuif, France, presented the update on the Trop-2-directed antibody–drug conjugate at the ESMO Virtual Congress 2020, following on from the initial phase II trial results that were reported in 2019.
“The final results of the TROPHY-U-01 cohort 1 confirm the interim findings and prior phase I/II study results and demonstrate that SG is generally well tolerated and has significant anticancer activity in heavily pretreated metastatic urothelial cancer patients who progressed on both platinum-based chemotherapy and checkpoint inhibitors”, the presenter summarised.
At data cutoff in May 2020, treatment was ongoing in 14% of the 113 patients given SG 10 mg/kg on days 1 and 8 of a 21-day cycle, while the majority had discontinued treatment because of progressive disease (66%), adverse events (7%), withdrawal of consent (6%) or death (3%).
After a median follow-up of 6.3 months, the mediation treatment duration was 3.7 months, up to a maximum of 16.0 months.
The objective response rate (ORR) was 27% including a complete response in 5%, and this met the primary endpoint of an ORR above 12%, Yohann Loriot said.
The median duration of response was 5.9 months, median progression-free survival (PFS) was 5.4 months and median overall survival (OS) was 10.5 months. The presenter commented that the OS may be an “underestimate” as treatment and responses are ongoing in eight of the 31 responding patients.
Yohann Loriot remarked that these outcomes “compare favourably with single-agent chemotherapy in this population”, which has a typical reported response rate of around 10%, a PFS of 2–3 months and OS of 7–8 months.
The most common treatment-related adverse events were diarrhoea, affecting 65% of patients, followed by nausea (58%), fatigue (50%) and alopecia (47%), although these effects were mostly at grade 3 or below.
Forty-six percent of patients experienced neutropenia, including 22% at grade 3 and 12% at grade 4, while the corresponding rates of febrile neutropenia were 10%, 7% and 3%. Neutropenia was managed by dose reduction or delay, and with the use of granulocyte colony-stimulating factor in 30% of patients.
Yohann Loriot noted that while neutropenia was reversible, half of the treatment discontinuations were related to neutropenia and there was one treatment-related death from sepsis linked to febrile neutropenia.
The presenter concluded that “SG has received fast track designation for this indication and may have the potential to change practice in this setting.”
The phase III confirmatory TROPiCS-04 trial is now underway in patients with unresectable locally advanced or mUC who have progressed after platinum-based chemotherapy and anti-PD-1 or PD-L1 therapy or if they have advanced within 1 year of neoadjuvant platinum and checkpoint inhibitor therapy.
The trial will compare SG 10 mg/kg dosage with a physician’s choice of docetaxel, paclitaxel or vinflunine and the primary endpoint will be OS.
LBA24 - Loriot Y, Balar AV, Petrylak DP, et al. Final results from TROPHY-U-01 cohort 1: A phase 2 open-label study of sacituzumab govitecan (SG) in patients with metastatic urothelial cancer (mUC) and disease progression after platinum (PLT)-based regimens and checkpoint inhibitors (CPI). Ann Oncol 2020; 31(Suppl 4): S1142–S1215. DOI: 10.1016/annonc/annonc325.
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