Editor's note: Please check back on Oct. 22 when the full data of EV-302 are presented at ESMO 2023.
Four weeks ago, Seagen and Astellas made waves when they revealed that the pairing of Padcev with Merck’s oncology superstar Keytruda had achieved improved outcomes over standard of care in patients with previously untreated bladder cancer.
The report was a bit of a tease, however, as the companies did not put numbers to the claim. Those highly anticipated figures are now in for the EV-302 phase 3 trial, and they lend more credence to the idea that the combo has the potential to be “practice-changing,” in the words last month of Seagen R&D chief Roger Dansey, M.D.
The results have been released ahead of the European Society for Medical Oncology (ESMO) Congress, which kicks off Friday in Madrid.
In the trial of 886 bladder cancer patients who were eligible for cisplatin or carboplatin-containing chemotherapy, the Keytruda-Padcev combination reduced the risk of death by 53% over chemo, according to a late-breaking ESMO abstract.
The median overall survival (OS) result for combo regimen patients was 31.5 months, compared to 16.1 months for those on chemotherapy.
The combo produced similar success in progression-free survival (PFS), reducing the risk of disease progression or death by 55%. Patients on the combo regimen lived a median of 12.5 months without progression, versus 6.3 months for the chemo arm.
Investigators will present the full trial results—along with commentary—Sunday at ESMO.
As for objective response rate in EV-302, the combo triggered a response in 67.7% of patients. That compared with 44.4% in the chemo arm.
The combo's safety profile won out, as well, as severe treatment-related adverse events were seen in 55.9% of patients. Of those on chemo, 69.5% experienced a grade 3 adverse event or worse.
A side effect concern with Padcev as a solo agent has been peripheral neuropathy. In EV-302, it was seen at a grade 3 level or higher in 6.8% of patients.
The most common adverse event for those on the combo was skin reactions, with 15.5% experiencing that complication.
The results could open the combo up to patients who are eligible for cisplatin-based chemotherapies, regardless of their PD-L1 status. In April, the combo won an FDA accelerated approval to treat first-line cisplatin-ineligible patients.
The inclusion of the cisplatin-eligible population on the combo's label could nearly double the addressable market for Padcev to more than $5 billion worldwide, William Blair analysts wrote last month.
While the data indicate that the Keytruda-Padcev combo can be transformative, there still is much to be determined about its effectiveness, according to analysts at Leerink Partners.
“For Padcev-Keytruda to become the standard-of-care, we believe the combination will need to demonstrate benefit across subgroups, with outcomes that exceed that achieved with platinum-based chemotherapy,” Leerink wrote last month.
One of the subgroups will be those who were provided Merck KGaA’s Bavencio for maintenance. The treatment was approved for bladder cancer during the trial.
Another key figure from EV-302, according to Leerink analyst Andrew Berens, M.D., prior to the data release, is the hazard ratio, which is the probability of a death or disease progression in the treatment group relative to that in a control group over a unit of time.
The hazard ratios were 0.47 for OS—which translates into the 53% death risk reduction—and 0.45 for PFS.
“I think we could see a hazard ratio below 0.5,” Berens told Fierce Pharma. “That would be big. That would be much improvement over the chemotherapy arm. And then we’ll be drilling down on the (cisplatin) eligible, (cisplatin) ineligible and patients who have gotten Bavencio maintenance.”