Urothelial Cancers Phase 3 Trial KEYNOTE-045 and KEYNOTE-361 Efficacy and Safety Results

Patrizia Giannatempo, MD from Fondazione IRCCS Istituto Nazionale dei Tumori ASCO 2023 abstract on Urothelial Cancers Phase 3 Trial KEYNOTE-045 and KEYNOTE-361 Efficacy and Safety Results.


Patrizia Giannatempo, MD, from the Fondazione IRCCS Istituto Nazionale dei Tumori, has conducted extensive research on the impact of histology on the efficacy and safety of pembrolizumab (pembro) monotherapy for advanced urothelial carcinoma (UC) in the phase 3 KEYNOTE-045 and KEYNOTE-361 trials. 

Urothelial carcinoma is the most common type of bladder cancer, and advanced cases are challenging to treat.

The KEYNOTE-045 trial was a landmark study evaluating the efficacy and safety of pembrolizumab compared to chemotherapy as a second-line treatment for advanced UC. The results of this trial demonstrated that pembrolizumab significantly improved overall survival and had a favorable safety profile when compared to chemotherapy. 

Notably, the clinical benefit of pembrolizumab was consistent across all histologic subtypes of UC, including transitional cell carcinoma, squamous cell carcinoma, and adenocarcinoma. These findings suggest that pembrolizumab can be an effective treatment option, regardless of the specific histology of the tumor.

In the subsequent KEYNOTE-361 trial, pembrolizumab was evaluated as both monotherapy and in combination with chemotherapy as a first-line treatment for advanced UC. The primary analysis of this trial revealed that pembrolizumab monotherapy did not significantly improve overall survival compared to chemotherapy. 

However, further exploration of the data based on histology provided valuable insights. It was observed that patients with squamous cell carcinoma who received pembrolizumab monotherapy had improved overall survival compared to those receiving chemotherapy. 

On the other hand, patients with transitional cell carcinoma did not experience a similar survival benefit with pembrolizumab monotherapy. These findings suggest that the histologic subtype of UC can influence the efficacy of pembrolizumab as a monotherapy, with squamous cell carcinoma demonstrating a more favorable response.

Dr. Giannatempo's research sheds light on the importance of considering histology when selecting treatment options for advanced UC. The efficacy of pembrolizumab appears to vary depending on the specific histologic subtype of the tumor. 

While pembrolizumab monotherapy showed consistent benefit across all histologic subtypes in the KEYNOTE-045 trial, the results from the KEYNOTE-361 trial highlight the need for a more nuanced approach. 

In cases of squamous cell carcinoma, pembrolizumab monotherapy may provide a survival advantage over chemotherapy, whereas transitional cell carcinoma may require alternative treatment strategies.

Overall, Dr. Giannatempo's research emphasizes the significance of personalized medicine in the field of oncology. Tailoring treatment decisions based on histology can lead to more effective and targeted therapies, optimizing patient outcomes in the management of advanced urothelial carcinoma. 

Further studies are warranted to explore the underlying mechanisms driving these differential responses and to develop strategies for improving the efficacy of pembrolizumab across all histologic subtypes of UC.