Dr Galsky on the Neoadjuvant Use of ICIs in Bladder Cancer

“Both [KEYNOTE-905 and KEYNOTE-B15] showed higher pCR rates, higher EFS and higher OS [with enfortumab vedotin plus pembrolizumab], marking a new era in the treatment of MIBC with a non–platinum-containing systemic therapy regimen.”

Matthew Galsky, MD, the director of Genitourinary Medical Oncology, co-director of the Center of Excellence for Bladder Cancer, the deputy director, and a professor of medicine (Hematology and Medical Oncology) at the Mount Sinai Tisch Cancer Center, discussed the emergence of immune checkpoint inhibitors (ICIs) the neoadjuvant setting of bladder cancer.

The role of immune checkpoint blockade in muscle-invasive bladder cancer (MIBC) has continued to expand beyond the adjuvant setting and is now firmly established in perioperative treatment strategies, Galsky began. Recent clinical trials have demonstrated that integrating immunotherapy into treatment before and after surgery can significantly improve outcomes, leading to major shifts in the standard of care for patients with MIBC, he said.

One of the most influential studies in this area has been the phase 3 NIAGARA trial (NCT03732677), which evaluated the addition of durvalumab (Imfinzi) to standard neoadjuvant gemcitabine and cisplatin chemotherapy prior to radical cystectomy, Galsky said. The trial showed that combining immunotherapy with platinum-based chemotherapy resulted in meaningful improvements across several key clinical end points. Patients receiving durvalumab experienced higher pathologic complete response (pCR) rates, improved event-free survival (EFS) outcomes, and superior overall survival (OS) compared with those treated with chemotherapy alone, he said. These findings provided strong evidence that immunotherapy can enhance the effectiveness of established neoadjuvant treatment regimens and improve long-term outcomes.

More recently, investigators have explored whether ICI-based regimens could further transform treatment in the perioperative setting. Two randomized phase 3 studies evaluated the combination of enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda) in patients with MIBC. The phase 3 KEYNOTE-905/EV-303 trial (NCT03924895) focused on patients who were ineligible for cisplatin-based chemotherapy and compared the combination regimen with radical cystectomy alone. Meanwhile, the phase 3 KEYNOTE-B15/EV-304 trial (NCT04700124) compared perioperative enfortumab vedotin plus pembrolizumab with the traditional approach of neoadjuvant gemcitabine and cisplatin followed by cystectomy in cisplatin-eligible patients.

Both studies demonstrated significant clinical benefits, including higher pCR rates, as well as improved EFS and OS outcomes, Galsky said. Collectively, the findings from NIAGARA and the enfortumab vedotin/pembrolizumab studies have ushered in a new era of MIBC management, expanding treatment options and redefining perioperative care for patients with this disease, he concluded.