Dr Galsky on the Integration of ICIs into the Bladder Cancer Treatment Landscape

“Enthusiasm for immune checkpoint blockade in this disease, similar to other malignancies, [stems from the] durable responses that can occur. [Additionally], many patients tolerate immune checkpoint blockade quite well.”

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) in bladder cancer.

Galksy began by noting that ICIs marked a turning point in the treatment of urothelial cancer and reinvigorated drug development efforts across the disease landscape. Initial studies demonstrated that PD-1 and PD-L1 inhibitors had meaningful activity as single agents in metastatic urothelial cancer, producing responses in approximately 20% to 30% of patients, he noted. Although response rates were modest, enthusiasm for these therapies stemmed from their ability to generate durable responses in some patients, often resulting in long-term disease control, he said. Additionally, many patients tolerated immune checkpoint blockade relatively well compared with traditional cytotoxic chemotherapy, despite the potential for immune-related adverse effects, he added.

The success of ICIs in the metastatic setting represented more than just a new treatment option; it provided the first major demonstration in years that a novel mechanism of action beyond chemotherapy could improve outcomes in urothelial cancer, Galsky said. This breakthrough renewed interest among researchers, investigators, and industry sponsors, creating new opportunities for therapeutic innovation not only with immunotherapy but also with other emerging treatment approaches, he added.

As is common in oncology drug development, investigators next sought to move immune checkpoint blockade into earlier stages of disease, where it might have a greater impact on long-term outcomes, Galsky said. The first definitive studies in muscle-invasive bladder cancer focused on the adjuvant setting, evaluating patients who had undergone radical surgery but remained at high risk for metastatic recurrence, he explained. Three similarly designed phase 3 trials were launched to assess one year of adjuvant PD-1 or PD-L1 blockade compared with placebo or observation, he said.

The results helped establish a new standard of care, according to Galsky. Although the phase 3 IMvigor010 trial (NCT02450331) failed to meet its primary end point, 2 other studies demonstrated significant clinical benefit, he said. Data from the phase 3 CheckMate 274 trial (NCT02632409) led to the FDA approval of adjuvant nivolumab (Opdivo) for high-risk patients following surgery, he added. Additionally, pembrolizumab (Keytruda) demonstrated benefit in the phase 3 AMBASSADOR trial (NCT03244384), he explained. Together, these findings validated the role of immune checkpoint blockade in earlier-stage bladder cancer and further expanded treatment options for patients with muscle-invasive disease, he concluded.