A recent study has demonstrated that current second-line treatments provide only modest benefits for patients with advanced bladder cancer who were previously treated with first-line enfortumab vedotin with pembrolizumab.
The study, published in the journal Bladder Cancer, utilized real-world data from a network of roughly 280 cancer clinics across the United States, representing both academic and community healthcare settings.
From a total of 15,236 patients with advanced urothelial carcinoma (the most common form of bladder cancer), the final cohort consisted of 118 patients who initiated second-line therapy between October 2021 and June 2025, after their cancer progressed on the first-line treatment approach enfortumab vedotin and pembrolizumab.
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A large group of patients returned to traditional chemotherapy, with 35% receiving carboplatin-based treatments and about 13% receiving cisplatin. Nearly 40% of patients fell into the category of “other therapies,” which include targeted drugs like erdafitinib, trastuzumab deruxtecan and sacituzumab govitecan. Interestingly, another 13% of patients were “rechallenged” with enfortumab vedotin, the same drug they had received in their first line of care.
To measure effectiveness, researchers tracked real-world time to next therapy, which measures the time from starting a second treatment until the cancer progresses enough to require a third type of therapy or until death. They also looked at real-world overall survival, which tracks the total time a patient lives from the start of their second-line treatment, regardless of the cause of death.
The researchers found that patients who were retreated with enfortumab vedotin stayed on the therapy the longest, with a median time of 8.5 months before needing a change. In comparison, those on carboplatin-based chemotherapy stayed on their treatment for a median of 4.7 months, while those on cisplatin-based therapy averaged 3.0 months.
Although the group receiving “other therapies” stayed on those specific drugs for a median of 3.9 months, they saw the longest overall survival, living for a median of 14.0 months. In contrast, those receiving carboplatin or cisplatin-based therapies had median survival times of 7.1 and 8.3 months, respectively.
These results align with a smaller study where platinum-based chemotherapy was used in up to 68% of cases, showing limited effectiveness.
Researchers addressed a recent expert survey and institutional review, which indicated that choosing the next treatment should increasingly depend on “biomarkers,” specific genetic markers found within the cancer cells. For instance, targeted therapies like erdafitinib are preferred for patients with a specific alteration in the fibroblast growth factor receptor 3 (FGFR3) gene. However, for the patients without such genetic markers, platinum-based chemotherapy remains the primary treatment choice despite its modest success.
As the largest real-world study of its kind, these results emphasize the need for more effective therapies and better evidence on how to sequence them. “These findings highlight the limited efficacy of current second-line treatment options in the post-EV + pembro setting, reveal the substantial heterogeneity of treatment patterns in clinical practice and underscore the urgent need for development of novel therapies and sequencing studies in this setting,” the study’s authors said.
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