medwireNews: Enfortumab vedotin may provide a platinum-free option for patients who have received prior immune checkpoint inhibitor (ICI) therapy for advanced urothelial carcinoma (UC) and are unable to tolerate cisplatin, suggest phase 2 trial findings.
As reported at the 2021 Genitourinary Cancers Symposium by Arjun Balar (NYU Langone Health, New York, USA), cohort 2 of the EV-201 study enrolled 89 individuals (median age, 75 years) with locally advanced or metastatic disease who had received prior PD-1 or PD-L1 inhibitor therapy but not platinum-based chemotherapy.
In these patients, treatment with enfortumab vedotin – a Nectin-4-directed antibody–drug conjugate – at a dose of 1.25 mg/kg on days 1, 8, and 15 of each 28-week cycle achieved an objective response rate (ORR) of 52%, including complete responses in 20%. The median duration of response was 10.9 months.
Subgroup analysis showed responses across most subsets of patients, including those with upper-tract primary tumors and liver metastases, at ORRs of 61% and 48%, respectively, as well as patients with no response to ICIs, at 48%.
Arjun Balar discusses the role of EV in earlier lines and stages of urothelial cancer (3:14).
Of note, the ORR was numerically higher among participants who did have a response to prior ICI treatment, at 64%, a finding that lends itself to two possible explanations, said Balar. “One is simply that patients who respond to treatment are ones who will respond to the next course of treatment,” he continued.
“The other and more tantalizing explanation is that there might be the presence of a synergy between both enfortumab vedotin and immunotherapy, and this is something that is actively being tested in randomized studies that are currently ongoing.”
After a median follow-up of 13.4 months, the median progression-free survival was 5.8 months and median overall survival was 14.7 months.
Treatment-related adverse events (TRAEs) of grade 3 or worse occurred in 55% of the cohort, and led to discontinuation in 16%.
Four deaths, three of which occurred within 30 days of initiation of enfortumab and in patients with a BMI of at least 30 kg/m2, were considered related to the study drug. Balar pointed out, however, that all four deaths were confounded by older age (≥75 years) and the presence of other comorbidities.
Arjun Balar discusses the treatment options for advanced urothelial cancer patients who progress on EV (1:05).
He also reported on some TRAEs of special interest, including skin reactions, peripheral neuropathy, and hyperglycemia, which occurred at a severity of at least grade 3 in 17%, 8%, and 6% of patients, respectively. Skin reactions and hyperglycemia developed quickly, after a median of 0.5 months, and resolved or improved in 80–89% of participants, while the median time to onset of peripheral neuropathy was 2.4 months and just over half the cases resolved or improved.
In conclusion, the presenter highlighted that the response rates to enfortumab in EV-201 “are numerically the highest observed for any regimen in cisplatin-ineligible patients with advanced [UC],” and the activity demonstrated in this cohort “builds upon the overall survival benefit shown in PD-1/PD-L1 inhibitor and platinum-treated patients in EV-301.”
He continued: “These data support continued investigation of [enfortumab] across the spectrum of [UC] and may support a new standard of care for this population with unmet need.”
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This independent news story was supported by an educational grant from Pfizer and Merck Healthcare KGaA, Darmstadt, Germany