medwireNews: The latest findings from the EV-103 study add support for the first-line use of enfortumab vedotin (EV) plus pembrolizumab in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer.
Jonathan Rosenberg (Memorial Sloan Kettering Cancer Center, New York, USA) presented data at the ESMO Congress 2022 in Paris, France, from the randomized noncomparative cohort K of the phase 1b/2 trial, which evaluated EV alone or alongside pembrolizumab in the first-line setting.
Jonathan Rosenberg presents data from a randomized noncomparative cohort of the EV-103 trial of enfortumab vedotin, investigating the agent alone or together with pembrolizumab as a first-line option for cisplatin-ineligible patients with advanced urothelial carcinoma (3:20).
He explained that EV monotherapy has previously shown antitumor activity in pretreated patients with advanced disease, while cohort A of EV-103 demonstrated promising efficacy of the combination in untreated cisplatin-ineligible patients.
The current presentation focused on the 149 participants of cohort K who were randomly assigned to receive EV 1.25 mg/kg on days 1 and 8 of each 3-week cycle in combination with pembrolizumab 200 mg on day 1 or as a single agent. Participants had locally advanced or metastatic urothelial cancer and were ineligible to receive cisplatin, primarily (60–63%) due to a creatinine clearance rate below 60 mL/min but no lower than 30 mL/min.
Stressing the noncomparative nature of the cohort design, Rosenberg reported a confirmed objective response rate (ORR) by blinded independent review of 64.5% with EV plus pembrolizumab and 45.2% with EV alone. Complete responses occurred in 10.5% and 4.1% of patients, respectively, and partial responses in 53.9% and 41.1%.
At the time of analysis, the median duration of response was unreached in the EV plus pembrolizumab group and was 13.2 months in the EV alone group. Responses were ongoing at 12 months in 65.4% of patients with a response to EV plus pembrolizumab and 56.3% of responders to EV monotherapy.
The median progression-free survival times were unreached and 8.0 months in the combination and EV monotherapy arms, respectively, while the median overall survival durations were 22.3 and 21.7 months.
The investigator noted, however, that the median follow-up was short – at a respective 14.8 and 15.0 months – and therefore “these data are expected to evolve significantly during follow-up.”
Turning to the safety data, Rosenberg said that the incidence of treatment-related adverse events of at least grade 3 was higher with the combination than with EV alone, at rates of 63.2% and 47.9%, respectively, but that “no new safety concerns emerged.”
He highlighted that skin reactions were observed more frequently with EV plus pembrolizumab than with EV alone, with events of grade 3 or worse occurring in 21.1% versus 8.2% of participants. Maculo-papular rash of this severity was experienced by a respective 17.1% and 1.4%.
In his concluding remarks, the presenter noted that EV plus pembrolizumab “is being further investigated in three ongoing phase 3 trials – the confirmatory trial for this study is EV-302 in cisplatin-eligible or ineligible patients with metastatic urothelial cancer randomized to chemotherapy or EV and [pembrolizumab].”
Rosenberg believes that the combination of EV and pembrolizumab “has the potential to become a first-line therapeutic option for cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer.”
Session discussant Laurence Albiges, from Gustave Roussy in Villejuif, France, outlined her take-home messages from the data, including the fact that the response to EV plus pembrolizumab in this cohort is consistent with what has been reported previously in cohort A, “showing a very strong response,” with an ORR above 60%.
At the same time, the activity of single-agent EV in the first line is “very similar” with that seen in the pivotal phase 3 trials of the agent in the second- and later-line settings.
Albiges questioned, however, whether this study of EV plus pembrolizumab is “enough to define the contribution of the components,” and she urged the audience to wait for the results of the phase 3 EV-302 study, which she believes will provide clarity on the risk–benefit ratio of the combination and “define if this regimen needs to be [a] new standard of care.”
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This independent news story was supported by an educational grant from Pfizer and Merck Healthcare KGaA, Darmstadt, Germany