Editor's Note: For many years, platinum-based chemotherapy has been the standard treatment for metastatic urothelial carcinoma. However, this year’s EV-302/KEYNOTE-A39 study results, published in the New England Journal of Medicine (NEJM), demonstrated that the combination of enfortumab vedotin and pembrolizumab (EV+P) significantly improves survival outcomes for patients with locally advanced or metastatic urothelial carcinoma. The 2024 ASCO Breakthrough conference, held from August 8-10 in Yokohama, Japan, presented the efficacy and patient-reported outcomes (PROs) from the KEYNOTE-A39 study. Here is a summary for our readers.In the Phase 3 EV-302 trial, the experimental treatment combination of EV+P for patients with previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC) significantly extended overall survival (OS) to 31.5 months and progression-free survival (PFS) to 12.5 months, compared to 16.1 months and 6.3 months, respectively, in the platinum-based chemotherapy group. The study also provided an in-depth analysis of patient-reported outcomes (PROs).
Patients in the study were randomly assigned in a 1:1 ratio to either the EV+P treatment group or the platinum-based chemotherapy group. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the Brief Pain Inventory Short Form (BPI-SF) were used to assess patients’ quality of life and pain levels at baseline and throughout treatment. The results showed that the median time to pain progression (TTPP) was 14.2 months in the EV+P group, compared to 10.0 months in the platinum-based chemotherapy group. Although there was no statistical difference in TTPP between the two groups, the EV+P group showed greater improvement in the reduction of the worst pain intensity at week 26 of treatment.
For patients with moderate to severe pain at baseline, the EV+P treatment showed significant pain improvement from week 3 to week 26. On the EORTC QLQ-C30 Global Health Status/Quality of Life (GHS/QoL) scores, the EV+P group initially experienced a slight decline in the early stages of treatment but returned to baseline levels, while the platinum-based chemotherapy group showed a continuous decline.
Additionally, the median time to confirmed deterioration (TTCD) was 5.9 months in the EV+P group, compared to 3.2 months in the platinum-based chemotherapy group, indicating that the EV+P treatment had an advantage in maintaining quality of life.
In summary, the EV+P treatment not only improved the survival rates of la/mUC patients but also preserved their quality of life and functional status, demonstrating its value in treatment. However, patient adherence, particularly following disease progression, was lower than expected, which may have influenced the study results, especially in the platinum-based chemotherapy group.
