EV-302 and CheckMate 901: Comparing the Practice-Changing ESMO Data for Metastatic UC

Live from the ESMO Congress 2023, Brad McGregor, MD, Dana-Farber Cancer Institute, and Guru P. Sonpavde, MD, AdventHealth Cancer Institute, share their thoughts on how the data compare across the CheckMate 901 and EV-302 studies for nivolumab plus gemcitabine-cisplatin versus EV plus pembrolizumab, as well as what considerations physicians should have when recommending these combinations to patients.

How do the data compare across the CheckMate 901 and EV-302 studies for nivolumab plus gemcitabine-cisplatin versus EV plus pembrolizumab?

Dr. McGregor: For decades, cisplatin has been the standard in metastatic bladder cancer. However, 2 recent studies have shown that new regimens have outperformed platinum-based therapy in a randomized setting. After the presentation of EV-302, there was even a standing ovation for the data.

Let’s start with the cis-gem and nivolumab data. Previous studies have not shown consistent benefits from adding immunotherapy to platinum-based regimens. However, there was a hint that patients receiving cisplatin might benefit from immunotherapy. So, this trial focused on patients receiving cisplatin and gemcitabine, randomized to receive cis/gem or cis/gem with nivolumab. The addition of nivolumab improved overall survival and progression-free survival, as well as reduced the rate of disease progression. Moreover, patients receiving nivolumab could tolerate more cycles of cisplatin, resulting in a remarkable complete response rate of around 20%. The median duration of complete response has not been reached and is already well over 37 months.

At the same session, we had the EV-302 trial, which compared EV plus pembrolizumab to platinum doublet therapy. EV pembro achieved a 70% response rate with a 30% complete response rate, which is unprecedented. Progression-free survival doubled, and overall survival improved significantly, reaching over 31 months. This is very exciting data.

What are the considerations that physicians should have when recommending these combinations to patients? Is there data still to come that will alter how these therapies are recommended?

Dr. Sonpavde: These results indeed represent a significant advance in the field. EV pembrolizumab achieved a median survival of 31.5 months across patient groups, regardless of cisplatin eligibility. The complete response rate was 29%, and the median duration of response seems to be extending beyond 2 years, although we await further data. Gem-cis nivolumab also showed an impressive 22% complete response rate with a mature median duration of complete response at around 37 months. This suggests that in patients likely to achieve complete response with cisplatin-based chemotherapy, gem-cis nivolumab might be a viable alternative to EV pembrolizumab. There are also important considerations like toxicity and cost differences to take into account.

Dr. McGregor: Absolutely, the potential for a complete response with gem-cis nivolumab and the subsequent discontinuation of gemcitabine makes it a compelling option. Additionally, it may be more suitable for patients who are frail or have a poor performance status. While these therapies offer great promise, further work is needed to identify biomarkers for patient selection and to manage potential toxicities, including those associated with EV pembrolizumab and gem-cis nivolumab.

Dr. Sonpavde: Indeed, more research is necessary to refine patient selection and explore biomarkers. Biomarkers like I2ERCCC2, which has been valuable in neoadjuvant cisplatin-based chemotherapy, may play a role in identifying patients who would benefit from GemCis nivo. We should also investigate whether there are biomarkers for predicting toxicities with these agents. The data we’ve seen is incredibly exciting and has the potential to redefine the landscape of metastatic bladder cancer.

View their next remarks on THOR, DAD, and Other Trials of Note.