The rising bladder cancer star that is the combination of Pfizer and Astellas’ Padcev and Merck’s Keytruda is looking to set a new standard in another patient group after proving its prowess as a pre- and post-surgery treatment in certain muscle-invasive bladder cancer (MIBC) patients.
The union of Merck’s anti-PD-1 and Pfizer and Astellas’ antibody-drug conjugate (ADC) chalked up a win at the first interim efficacy analysis of a phase 3 study, known both as EV-303 and Keynote-905, of MIBC patients who are not eligible for or declined cisplatin-based chemotherapy, the companies said Tuesday.
When given before and after radical cystectomy surgery, Padcev plus Keytruda achieved a statistically significant and clinically meaningful improvement in event-free survival, plus hit on its secondary endpoints of overall survival and pathologic complete response rate, when compared to surgery alone.
It marks the first positive phase 3 study to improve survival in cisplatin-ineligible MIBC, according to Merck. The results underscore the drug combo’s “practice-changing potential” in earlier stages of bladder cancer, Pfizer’s oncology chief development officer Johanna Bendell, M.D., noted in a release.
“These results from EV-303 represent a breakthrough for cisplatin-ineligible patients with muscle-invasive bladder cancer, demonstrating the potential of Padcev in combination with Keytruda when used before and after surgery as a new standard of care,” Astellas’ head of oncology development Moitreyee Chatterjee-Kishore, Ph.D., added.
The companies plan to discuss the results with regulatory authorities worldwide and present them at an upcoming medical meeting.
The trial has a third arm, in which patients receive Keytruda alone around surgery. The study is still ongoing to evaluate the three endpoints for that arm against surgery.
Meanwhile, another study of the perioperative Padcev-Keytruda combo, coded EV-304 or Keynote-B15, is focused on the cisplatin-eligible population.
Cisplatin-based chemotherapy, followed by surgery, is the standard treatment for MIBC, but up to half of patients are ineligible for cisplatin, leaving limited treatment options. MIBC makes up 30% of all bladder cancer cases, according to Pfizer.
The Padcev-Keytruda combo has already made a significant mark on the bladder cancer space. The duo first got a broad FDA approval for first-line locally advanced or metastatic urothelial cancer after proving it could slash the risk of death by 53% compared to chemotherapy, results that earned a standing ovation at that year’s European Society for Medical Oncology Congress (ESMO). The approval made the combo therapy the first regimen for advanced bladder cancer that showed superiority to platinum chemotherapy, the gold standard for decades.
Since then, Keytruda on its own cut down the risk of disease recurrence when used after surgery in high-risk patients with localized muscle-invasive bladder cancer and locally advanced bladder cancer, but fell short of a mature overall survival benefit. The drug has a clutch of existing bladder cancer nods, while Padcev is also approved as a single-agent treatment in certain bladder cancer patients.
Pfizer got its hands on Padcev through its $43 billion Seagen buyout. Astellas has estimated Padcev’s peak sales to hit between 400 billion to 500 billion Japanese yen ($2.7 billion to $3.4 billion).