Lennon and McCartney. Simon and Garfunkel. Richards and Jagger.
Padcev and Keytruda?
Can the cancer-fighting duo rock on in bladder cancer?
Data presented from the EV-302 phase 3 trial suggest that Seagen and Astellas’ antibody-drug conjugate Padcev and Merck’s oncology superstar Keytruda can make beautiful music together.
Four weeks ago, the companies made waves when they revealed that their combination achieved improved outcomes over standard of care in previously untreated bladder cancer patients.
The report was a bit of a tease, however, as the companies did not put numbers to the claim. Those highly anticipated figures were discussed Sunday in Madrid the at the European Society of Medical Oncology (ESMO) Congress, and they lend more credence to the idea that the combo has the potential to be “practice changing,” in the words of Seagen R&D chief Roger Dansey, M.D.
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.
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.
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 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.
“It’s rare that a trial comes along and really does offer that transformative element,” Dansey said in an interview with Fierce. “The initial data with Padcev and Keytruda was really eye-opening because it started to hint at the potential value of combining an ADC, using Seagen’s technology, together with a PD-1 inhibitor, such that you get the benefits of a highly active direct therapy, the ADC, together with immunotherapy intervention.”
Equally excited about the potential the combo can bring is Merck’s late-stage oncology chief Marjorie Green, M.D., who worked at Seagen when the idea was hatched.
“There are studies out there that you feel a joy to be a part of because you are helping to change therapy that’s going to rewrite textbooks,” Green said in an interview. “Sorry, I’m gushing. But when you have amazing data, it’s hard not to get a little giddy.”
The results could open the combo up to patients who are eligible for cisplatin-based chemotherapy, 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 a game changer in the indication, 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 (HR), which is the probability of a death or a 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.”