Dr Tagawa on the Rationale for Investigating First-Line Nivolumab Plus Cisplatin in Urothelial Cancer

Scott T. Tagawa, MD, MS, FACP, FASCO, professor of medicine and urology at Weill Cornell Medicine, and an attending physician at NewYork-Presbyterian–Weill Cornell Medical Center, discusses the evolution of anti-PD1– based regimens in advanced urothelial cancer, and the rationale for evaluating nivolumab (Opdivo) plus cisplatin in the first-line setting for this disease.

In advanced urothelial carcinoma, the use of PD-1/PD-L1 inhibitors has been a pivotal treatment approach, particularly in platinum-refractory disease where these agents initially demonstrated efficacy, Tagawa begins. Pembrolizumab (Keytruda) emerged as the standard of care in this setting, inducing a survival benefit in a variety of combination regimens, he says. Accordingly, research efforts shifted to focus on moving treatment with anti-PD1 agents into the first-line setting, Tagawa explains. Several initial trials with various combinations did not meet their primary end point. However, among these investigations, treatment with avelumab (Bavencio) maintenance proved successful in extending benefits with first-line therapy as long as the patient did not experience progression, Tagawa says.

Interestingly, preclinical and clinical data suggest that cisplatin may possess greater immunogenicity compared to carboplatin, Tagawa continues. This led to a significant development where, for the first time in the frontline setting, the immune checkpoint inhibitor nivolumab was combined with cisplatin-based chemotherapy, Tagawa reports. Findings from the phase 3 CheckMate 901 trial (NCT03036098) showed that nivolumab combination produced a median overall survival of 21.7 months (95% CI, 18.6-26.4) vs 18.9 months (95% CI, 14.7-22.4) with chemotherapy alone (HR, 0.78; 95% CI, 0.63-0.96; P = .0171). Based on these data, the FDA approved first-line nivolumab plus cisplatin and gemcitabine for patients with unresectable or metastatic urothelial cancer on March 7, 2024.

This approach underscores the importance of understanding the immunogenic properties of different chemotherapies and leveraging them to enhance the efficacy of immunotherapy in the frontline setting. Such developments provide clinicians with more options and opportunities to optimize treatment strategies for patients with advanced urothelial carcinoma.