Merck’s Keynote-361 study in newly diagnosed metastatic bladder cancer asked a key question: Could adding Keytruda to chemo improve on chemo, the standard of care?
The answer was no.
But “that’s not to say that there was no activity” in the Keytruda arm, Scot Ebbinghaus, Merck's vice president of clinical research, said.
On the contrary, “there was certainly a trend” toward life extension with the Keytruda-chemo combo; the tandem reduced patients’ risk of disease progression or death by 22% and their risk of death by 14%.
“They just didn’t reach quite the magnitude that was needed to show statistical significance,” Ebbinghaus said.
There were a couple factors at play that “may have reduced our ability to detect a significant improvement in overall survival,” he noted. For one, almost half of patients in the solo chemo arm did get an anti-PD-1 therapy of some kind—“and in some cases, that was actually even without having documented disease progression,” Ebbinghaus said.
The trial also asked an “even bolder” question, which was whether Keytruda could replace chemo altogether. While Keytruda wasn’t formally tested against chemo, “it does not look like (Keytruda) would have been superior,” Ebbinghaus said, with Merck’s superstar cutting the risk of death by just 8%.
The good news for Keytruda? It spurred longer-lasting responses to treatment than chemo did, with patients responding for about 28 months, compared with about six months for those on chemo. Keytruda’s number of serious side effects was lower, too.
Thanks to those positives, Merck doesn’t see the trial as undermining Keytruda monotherapy in its currently approved metastatic bladder cancer uses as a second-line treatment post-chemo and as a first-line treatment for chemo-ineligible patients.
And the company isn’t slowing down in the search for new indications, either. It’s testing Keytruda in early disease and in non-muscle invasive bladder cancer, and as part of a combo with Astellas and Seattle Genetics’ Padcev in previously untreated metastatic patients.
“I think in the overall picture, it’s one negative study, but we have a lot of other reason to believe that Keytruda has an important role to play in bladder cancer, including in the already approved indications as well as in our future development program,” Ebbinghaus said.
Meanwhile, Keytruda wasn’t the only member of the PD-1/PD-L1 class to come up short in a metastatic bladder cancer trial presented at the European Society for Medical Oncology's virtual congress. AstraZeneca’s Imfinzi and Imfinzi-tremelimumab pairing both failed to top chemo in the phase 3 Danube study.