Nivolumab plus chemotherapy is the first combination to outperform chemotherapy alone as first-line treatment for unresectable or metastatic urothelial cancer.
Cisplatin-based chemotherapy has been the first-line standard of care for cisplatin-eligible patients with unresectable or metastatic urothelial carcinoma for decades. Durable responses to first-line chemotherapy are rare. Prior attempts to improve this treatment by combining chemotherapy concurrently with an immune checkpoint inhibitor have been unsuccessful.1,2 The current randomized phase 3 CheckMate901 trial (NCT03036098) combined chemotherapy (gemcitabine/cisplatin) with nivolumab for the treatment of unresectable or metastatic urothelial cancer. Results were presented by Dr. Michiel van der Heijden of the Netherlands Cancer Institute, Amsterdam.3 The CheckMate901 trial enrolled 608 participants with previously untreated unresectable or metastatic urothelial cancer, who were randomized 1:1 to gemcitabine/cisplatin for 6 cycles or nivolumab plus gemcitabine/cisplatin for 6 cycles followed by nivolumab until disease progression or a maximum of 1 year. The primary endpoints were progression-free survival (PFS) and overall survival (OS).
Nivolumab plus chemotherapy significantly outperformed chemotherapy alone both for PFS and OS. Median OS was 21.7 months for nivolumab plus chemotherapy versus 18.9 months for chemotherapy alone (HR, 0.78; 95% CI, 0.63-0.96; P=.0171); median PFS was 7.9 months versus 7.6 months (HR, 0.72; 95% CI, 0.59-0.88; P=.0012). The objective response rate (ORR) was also improved in the nivolumab arm, represented by ORRs of 57.6% (21.7% complete responders) versus 43.1% (11.8% complete responders). Responses were rapidly achieved (median time-to-response 2 months in both arms) and the median duration of response was longer in the nivolumab arm (9.5 months vs 7.3 months in the control arm). The median duration of complete response was 37.1 months in the nivolumab arm versus 13.2 months in the control group.
The rate of treatment-related adverse events was almost similar in both arms: 57% versus 48% (any grade) and 22% versus 18% (Grade ≥3). The most prominent adverse events were chemotherapy-related, and health-related quality of life was stable and comparable in both arms.
“Nivolumab plus gemcitabine/cisplatin is the first chemo/immune therapy combination to beat chemotherapy alone as a first-line treatment option for patients with unresectable or metastatic urothelial cancer,” concluded Dr. van der Heijden. “These results support nivolumab plus gemcitabine/cisplatin to become a new standard of care for these patients.
Copyright ©2023 Medicom Medical Publishers
