Data from the phase 1b/2 trial of Padcev in combination with Keytruda displayed promise for patients with metastatic urothelial carcinoma, but further research is needed.
The combination of Padcev (enfortumab vedotin-ejFv) and Keytruda (pembrolizumab) showed a 71% objective response rate (the proportion of patients with a tumor size reduction) in patients with advanced or metastatic urothelial carcinoma in data presented at the 2019 European Society of Medical Oncology conference, however, updated data at the 2020 Genitourinary Cancers Symposium showed an increase of the objective response rate to 73%.
“(The patients’) responses (to the therapy) did not matter whether PDL1 status was high or low, it was essentially the same response rate regardless of that,” said Dr. Jonathan E. Rosenberg in an interview with CURE
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®. Moreover, patients in this study were cisplatin ineligible and typically have a poor prognosis with carboplatin-based chemotherapies with a progression free survival of about 6 months, Rosenberg, chief, Genitourinary Medical Oncology Service, Memorial Sloan Kettering Cancer Center, explained.
Keytruda is an antibody immunotherapy that blocks the PD-1 and PD-L 1 (proteins found on T cells), which are pathways where cancer cells often hide from the T-cells that are created in the immune system to fight them. Padcev is also an antibody drug that attaches to cancerous cells and delivers cell killing medicine. In combination, they have a favorable response that is comparable to rates of chemotherapy used in patients with metastatic urothelial carcinoma.
“In this study the progression free survival was actually 12.3 months, the median overall survival has not yet been reached, and the 1 year survival landmark analysis at this time point shows that 86% of patients are still alive at one year, which is a very impressive statistic in the context of the disease,” said Rosenberg. The study also showed that the 1-year overall survival rate was 81.6%.
However, Rosenberg was quick to note that the trial was only a 45-patient trial and that the trial needed to be expanded to see how more patients with metastatic urothelial carcinoma responded to the treatment. Moreover, he cited there needs to be a deeper understanding of how pre-trial treatments could play a role into a patient’s response.
A randomized phase 3 trial of Padcev and Keytruda is underway to compare the treatment to cisplatin and carboplatin-based chemotherapies for patients with advanced or metastatic urothelial carcinoma.