Emanuele Crupi, MD, highlights phase 2 trial of GemFLP in urinary tract adenocarcinomas

In this video, Emanuele Crupi, MD, discusses prospective phase 2 data evaluating frontline gemcitabine, 5-fluorouracil/leucovorin, and cisplatin (GemFLP) in patients with advanced urachal and non-urachal adenocarcinomas of the urinary tract.¹ Crupi is a postdoctoral fellow in medical oncology at MD Anderson Cancer Center in Houston, Texas.

Crupi explained that adenocarcinomas of the urinary tract are rare and biologically heterogeneous, with limited prospective evidence to guide frontline treatment. In this single-arm phase 2 study (NCT00082706), 46 patients with metastatic or unresectable disease received GemFLP, a triplet regimen consisting of gemcitabine, 5-fluorouracil/leucovorin, and cisplatin. Among all patients, 28 had unresectable urachal (UA) and 18 had non-urachal adenocarcinoma (NUA).

The objective response rate was 44% (20/46), with a median duration of response of 8.6 months (95% CI, 4.6 to 30.8). The median progression-free survival (PFS) was 3.3 months (95% CI, 2.3 to 8.4), and the median overall survival (OS) was 21.0 months (95% CI, 15.9 to 35.3), with no significant differences in PFS or OS between urachal and non-urachal adenocarcinoma (P = .39 and P = .99, respectively).

According to Crupi, these findings provide a prospective benchmark in a disease setting where established frontline standards are lacking.

The authors noted that toxicities were generally manageable, with anemia (28.1%), thrombocytopenia (21.9%), and neutropenia (12.5%) among the most common hematologic adverse events and dehydration (21.9%) the most frequent nonhematologic event.

Exploratory biomarker analyses found that higher baseline CA125 was associated with inferior overall survival (HR, 1.33; 95% CI, 1.12 to 1.58; P = .001), although Crupi emphasized that these findings require validation in larger prospective cohorts.

“I think that where we are heading next should be tailoring to the molecular profile [of] the patient, especially in this rare disease,” he noted.

He pointed to ongoing investigation of enfortumab vedotin-ejfv (Padcev) plus pembrolizumab (Keytruda) in histologic variants and the potential relevance of KRAS-directed therapies, given the prevalence of KRAS alterations reported in urachal adenocarcinoma. He concluded by describing GemFLP as a reasonable benchmark for the field, emphasizing that the findings underscore the need for continued prospective research and molecularly informed treatment approaches.

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