Recent research found that combining the platinum-based chemotherapy gemcitabine-cisplatin with the anti-programmed death 1 (PD-1) antibody nivolumab may benefit people with advanced urothelial cancer. This combination has significantly increased both overall and progression-free survival.
For patients with unresectable or metastatic urothelial carcinoma, platinum-based chemotherapy has long been the mainstay of treatment. For suitable patients, cisplatin-based chemotherapy has been preferred over carboplatin-based regimens. However, after cisplatin-based therapy, the median overall survival is only around 15 months, and long-term responses are exceedingly unusual. Â
Despite the success of cisplatin-based chemotherapy, there is still an urgent need for additional, similarly effective medications. As a first-line treatment for metastatic urothelial carcinoma, no new drug has been identified to improve survival when combined with platinum-based chemotherapy. However, the emergence of nivolumab as a second-line treatment for urothelial carcinoma after platinum-based chemotherapy has altered the game.Â
In the CheckMate 901 study, nivolumab coupled with gemcitabine-cisplatin produced better outcomes than gemcitabine-cisplatin alone. When compared to usual treatment, the combination therapy significantly improved overall survival and progression-free survival in people with advanced urothelial carcinoma who had never been treated previously.
The combination group showed a considerably higher proportion of complete responses (21.7% vs. 11.8%) than the standard therapy group. Despite the fact that the longest period of nivolumab therapy was 2 years, the median duration of full response in the combination group was more than three times longer than in the nivolumab group. Â
The safety profile of combination treatment is similar to the safety profiles of individual medications, which is encouraging. Therapy-related fatalities were rare, and there were no significant differences in health-related quality-of-life outcomes between the two groups. Â
Surprisingly, in some tumor types, a combination of immunotherapy and chemotherapy improves overall survival and progression-free survival more than either treatment alone. Previous phase 3 studies that combined platinum-based chemotherapy with novel drugs such as immune checkpoint inhibitors did not increase overall or progression-free survival. This differential might be attributed to variations in immunomodulatory activities between cisplatin and carboplatin. Â
The CheckMate 901 study especially investigated whether PD-1 inhibition was beneficial when combined with cisplatin-based treatment. Evidence from clinical trials shows that cisplatin-based chemotherapy, rather than carboplatin-based chemotherapy, may work better in combination with immune checkpoint suppression in the treatment of metastatic urothelial carcinoma. Â
For patients with advanced urothelial carcinoma who have not previously been treated, the combination of nivolumab and gemcitabine-cisplatin is extremely successful. This groundbreaking study presents solid evidence in favor of combining chemotherapy with an immune checkpoint inhibitor, ushering in a new era in the treatment of this difficult disease. Â
Journal ReferenceÂ
van der Heijden, M. S., Sonpavde, G., Powles, T., Necchi, A., Burotto, M., Schenker, M., … Galsky, M. D. (2023). New England Journal of Medicine. doi:10.1056/nejmoa2309863Â
