(UroToday.com) The 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) cancers symposium held in San Francisco, CA between January 25th and 27th was host to a urothelial carcinoma poster session. Dr. Cindy Jiang presented an analysis of the UNITE database evaluating the sequencing of erdafitinib and enfortumab vedotin in patients with fibroblast growth factor receptor (FGFR2/3) altered advanced urothelial cancer.
The optimal therapy sequencing in locally advanced, metastatic urothelial carcinoma with FGFR2/3 alterations remains unclear. Thus, additional data is needed to inform decision-making. There is evidence that FGFR inhibition may increase Nectin-4 expression, and thus agents such as erdafitinib (FGFR inhibitor) may have a synergistic mechanism of action with enfortumab vedotin (antibody-drug conjugate targeting Nectin-4).
The investigators thus hypothesized that outcomes with enfortumab vedotin would be more favorable when given following erdafitinib, compared to prior to erdafitinib, in patients with locally advanced/metastatic urothelial carcinoma patients harboring susceptible FGFR2/3 genomic mutations.
UNITE is a multi-institutional retrospective database including patients from 16 US sites who received systemic therapy for locally advanced/metastatic urothelial carcinoma.
The study endpoints were:
- Overall survival (OS) recorded from erdafitinib or enfortumab vedotin start (whichever administered first)
- Progression-free survival (PFS), measured from EV administration
These outcomes were assessed using Kaplan Meier curves, with between group comparisons performed using the log-rank test. Cox proportional hazards regression modeling was performed to adjust for potential confounders. Univariable analyses were performed initially, and variables for the final model were selected using the univariable screening approach whereby variables with a p-value <0.2 were included in the final model. Continuous and categorical variables were compared using Wilcoxon rank sum and Fisher's exact tests. The objective response rates (ORR) were compared using the Chi-square test.
The investigators identified 94 patients with FGFR2/3 alterations, of whom 24 received erdafitinib followed by enfortumab (‘experimental group’) and 15 received enfortumab vedotin followed by erdafitinib (‘control group’). The median patient age was 72 years. 65% of patients had primary bladder tumor and 73% had pure urothelial histology. 60% of patients had visceral metastases (23% liver metastases). With regards to prior treatments, 93% had received prior immunotherapy and 63% had received prior platinum-based chemotherapy. Patients in the enfortumab vedotin 1st group had a higher proportion of patients with ECOG performance status 0 – 1 (94% versus 67%, p=0.04).
The efficacy outcomes were as follows:
- ORR:
- Erdafitinib to enfortumab vedotin: 32%
- Enfortumab vedotin to erdafitinib: 67% (p=0.04 for comparison of two sequences)
- Enfortumab vedotin only: 49%
- OS (median)
- Erdafitinib to enfortumab vedotin: 21 months
- Enfortumab vedotin to erdafitinib: 19 months
- Enfortumab vedotin only: 12 months
On multivariable analysis, there was no difference in overall survival between the two treatment combination sequences.
Dr. Jiang concluded that there was no difference in overall survival between patients who receive erdafitinib followed by enfortumab vedotin compared to the reverse sequence, but overall survival for both was superior to enfortumab vedotin alone, which may simply reflect selection and time biases. The sequencing of enfortumab vedotin and erdafitinib appears to be less important as long as patients with susceptible FGFR2/3 alterations receive both agents at some point.
Presented by: Cindy Y. Jiang, MD, Clinical Fellow, Department of Hematology and Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Written by: Rashid Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2024 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, San Francisco, CA, January 25th – January 27th, 2024