Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: The EV-201 trial findings indicate that the nectin-4-directed antibody–drug conjugate enfortumab vedotin (EV) may offer a novel option for advanced urothelial cancer patients who are unsuitable for cisplatin chemotherapy and have already received an immune checkpoint inhibitor (ICI).
Presenting the phase II results at the 2021 Genitourinary Cancers Symposium, Arjun Balar, from Perlmutter Cancer Center at NYU Langone Health in New York, USA, said the response rates “are numerically the highest observed for any regimen in cisplatin-ineligible patients with advanced urothelial carcinoma.”
Cohort 2 of the study included 89 patients aged a median 75 years (74% male) who had locally advanced or metastatic urothelial carcinoma, were naïve to platinum chemotherapy and ineligible for cisplatin treatment but had previously received a PD-1 or PD-L1 inhibitor, most commonly as a first-line treatment (98%).
Patients were given EV at a dose of 1.25 mg/kg on days 1, 8 and 15 of each 28-day cycle for a median of 6 months, discontinuing treatment for progressive disease (51%), adverse events (24%) or other reasons.
Overall, 52% had a RECIST response by blinded independent central review after a median 1.8 months, including a complete response in 20% and a partial response in 31%, while 30% had stable disease, reported Arjun Balar.
He emphasised that responses to EV were reported across all patient subgroups including in individuals whose primary tumours occurred in the upper tract or bladder, patients with or without liver metastases, and those who had and had not responded to ICI therapy.
Responses lasted for a median of 10.9 months; progression-free survival was a median of 5.8 months and overall survival 14.7 months, with 29% of patients continuing to be followed up in the study after a median of 13.4 months.
Treatment-related adverse events (TRAEs) led to EV discontinuation in 16% of patients, most commonly due to peripheral neuropathy (4%). Grade 3 or more severe TRAEs occurred in 55%, including neutropenia (9%), maculo-papular rash (8%) and fatigue (7%).
There were three treatment-related deaths within 30 days of first EV dose from acute kidney injury, metabolic acidosis and multiple organ dysfunction syndrome, respectively, and a fourth death from pneumonitis at a later time point. All deaths were “confounded by age (≥75 years) and other comorbidities”, the investigator observed.
TRAEs of special interest at any grade included skin reactions in 61% of patients, peripheral neuropathy in 54% and hyperglycaemia in 10%, with improvement or resolution reported for 80%, 56% and 89% of these groups, respectively, at time of last follow-up.
Arjun Balar summarised that EV had a “[t]olerable safety profile in an elderly patient population ineligible for cisplatin”.
The presenter concluded: “Activity demonstrated in EV-201 Cohort 2 builds upon the overall survival benefit shown in PD-1/PD-L1 inhibitor and platinum-treated patients in EV-301.
“These data support continued investigation of EV across the spectrum of urothelial carcinoma and may support a new standard of care for this population with unmet need.”
Balar AV, McGregor BA, Rosenberg JE, et al. EV-201 Cohort 2: Enfortumab vedotin in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer who received prior PD-1/PD-L1 inhibitors. J Clin Oncol 2021; 39 (suppl 6; abstr 394). DOI: 10.1200/JCO.2021.39.6_suppl.394
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