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.
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.
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.
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.
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.
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.
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.
Journal Reference
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/nejmoa2309863
