medwireNews: The phase 3 EV-301 trial has demonstrated significantly better overall survival (OS) with enfortumab vedotin than single-agent chemotherapy in advanced urothelial cancer (UC) patients who have previously received platinum-based chemotherapy and checkpoint inhibitors.
The data were published in The New England Journal of Medicine to coincide with their presentation at the 2021 Genitourinary Cancers Symposium by Thomas Powles, from Barts Cancer Institute in London, UK.
He told delegates that the nectin-4-targeted antibody–drug conjugate “is the first drug beyond chemotherapy and immune therapy to show a significant survival advantage” in this patient population.
“This is a big step in the right direction for patients with advanced urothelial cancer, where treatment options remain quite limited,” added Powles.
In the preplanned interim analysis, conducted at a median follow-up of 11.1 months, the primary endpoint of OS was a median of 12.88 months for the 301 patients who were randomly assigned to receive enfortumab vedotin 1.25 mg/kg on days 1, 8, and 15 of every 28-day cycle.
This was significantly longer than the median of 8.97 months for their 307 counterparts who instead received investigator’s choice of docetaxel 75 mg/m2, paclitaxel 175 mg/m2, or vinflunine 320 mg/m2 every 3 weeks, and equated to a 30% reduction in the risk for death with enfortumab.
The OS benefit was generally consistent across subgroups, although “some subgroups were too small to draw definitive conclusions,” said the presenter.
Enfortumab-treated patients also had significantly longer median progression-free survival and a higher objective response rate than those given chemotherapy, at 5.55 versus 3.71 months (hazard ratio=0.62) and 40.6% versus 17.9%, respectively.
Powles highlighted that “enfortumab vedotin demonstrated a tolerable and manageable safety profile,” with “no new safety signals.”
Grade 3 or worse treatment-related adverse events (TRAEs) occurred in about half the participants in the enfortumab and chemotherapy arms, and the rate of discontinuation due to any-grade TRAEs was a comparable 14.0% and 11.0%, respectively. In all, 2.4% of participants in the enfortumab group and 1.0% of those in the chemotherapy group experienced fatal TRAEs.
The incidence of maculopapular rash of at least grade 3 was higher among enfortumab- than chemotherapy-treated patients, at 7% versus 0%, but the rates of neutrophil count decreases (6 vs 13%), leukopenia (1 vs 7%), and febrile neutropenia (1 vs 5%) of this grade were lower.
TRAEs of special interest included skin reactions, peripheral neuropathy, and hyperglycemia, with grade 3 or more severe events reported in 15%, 5%, and 4% of the enfortumab group, respectively. But on the whole, such TRAEs tended to be “mild-to-moderate in severity,” commented Powles.
Discussing the results, Arlene Siefker-Radtke (The University of Texas MD Anderson Cancer Center, Houston, USA) remarked that “enfortumab vedotin now joins the ranks of multiple novel agents showing level 1 evidence for third-line use” in patients previously treated with platinum chemotherapy and checkpoint inhibitors.
“While it’s currently approved in the third-line setting, we’re all eager to await the outcomes of the front-line studies of enfortumab vedotin combined with pembrolizumab, which showed such a promising objective response rate as has been presented at earlier meetings,” she concluded.
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This independent news story was supported by an educational grant from Pfizer and Merck Healthcare KGaA, Darmstadt, Germany