Padcev (enfortumab vedotin) + Keytruda (pembrolizumab) First Line in Advanced Urothelial Cancer: What the EV-302 Trial Showed
The New England Journal of Medicine has published the results of the phase III EV-302 trial in patients with previously untreated locally advanced or metastatic urothelial cancer. The trial compared the combination of Padcev (enfortumab vedotin) + Keytruda (pembrolizumab) with standard platinum-based chemotherapy. The combination showed a clear advantage both in progression-free survival and in overall survival. Padcev and Keytruda are registered in Russia.
In brief: what happened
The trial enrolled 886 patients: 442 in the combination group and 444 in the chemotherapy group.
- In the control group, gemcitabine was used in combination with either cisplatin or carboplatin.
- Median progression-free survival was 12.5 months with the combination versus 6.3 months with chemotherapy.
- Median overall survival was 31.5 months versus 16.1 months, respectively.
Key numbers from the trial
The combination reduced the risk of progression or death by 55%: HR 0.45; 95% CI 0.38–0.54; p<0.001. The risk of death was reduced by 53%: HR 0.47; 95% CI 0.38–0.58; p<0.001. Grade 3 or higher adverse events were noted in 55.9% of patients in the combination group and in 69.5% in the chemotherapy group.
Why this matters in practice
Before EV-302, platinum-based chemotherapy remained the standard first-line treatment. This trial showed that the combination can deliver a clear benefit simultaneously in both progression-free survival and overall survival. For practice, this means that the discussion of first-line therapy has changed.
Limitations / what does not change yet
These results cannot be automatically applied to every clinical situation in cancer of the urinary tract. The trial concerned specifically previously untreated locally advanced or metastatic urothelial cancer. It is not a trial for muscle-invasive operable bladder cancer and not for adjuvant therapy after surgery.
When a second opinion is especially useful
- the diagnosis is already confirmed, but the first-line approach remains unclear;
- you are being offered only chemotherapy and you want to understand whether there is a more modern alternative;
- there are doubts about how well the chosen regimen matches the current data;
- doctors' opinions differ regarding the first line of treatment;
- it is important to assess not only the immediate stage, but the entire sequence of therapy.
What to prepare for the consultation
To make the conversation substantive, it is best to gather in advance:
- the histopathology report;
- a discharge summary indicating the stage and extent of the process;
- the latest CT, MRI or PET-CT;
- blood test results, including liver and kidney function markers;
- information about comorbidities;
- a list of all medications you are currently taking.
Frequently Asked Questions
Who is the combination suitable for according to this trial?
It concerns patients with previously untreated locally advanced or metastatic urothelial cancer.
Does this mean chemotherapy is no longer needed?
No. Chemotherapy remains an important treatment option. But after EV-302 the choice of first-line therapy has become broader.
Can treatment that has already started be changed urgently?
No. The decision depends on the stage of treatment, tolerance of therapy and the extent of the disease.
Are Padcev and Keytruda registered in Russia?
Yes. Both drugs have registered trade names in Russia.
More answers on the FAQ page.