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Background Enfortumab vedotin (EV) is a novel antibody‐drug conjugate approved for advanced urothelial cancer (aUC) refractory to prior therapy. In the Urothelial Cancer Network to Investigate Therapeutic Experiences (UNITE) study, the authors looked at the experience with EV in patient subsets of interest for which activity had not been well defined in clinical trials. Methods UNITE was a retrospective study of patients with aUC treated with recently approved agents. This initial analysis focused on patients treated with EV. Patient data were abstracted from chart reviews by investigators at each site. The observed response rate (ORR) was investigator‐assessed for patients with at least 1 post‐baseline scan or clear evidence of clinical progression. ORRs were compared across subsets of interest for patients treated with EV monotherapy. Results The initial UNITE analysis included 304 patients from 16 institutions; 260 of these patients were treated with EV monotherapy and included in the analyses. In the monotherapy cohort, the ORR was 52%, and it was >40% in all reported subsets of interest, including patients with comorbidities previously excluded from clinical trials (baseline renal impairment, diabetes, and neuropathy) and patients with fibroblast growth factor receptor 3 (FGFR3) alterations. Progression‐free survival and overall survival were 6.8 and 14.4 months, respectively. Patients with a pure urothelial histology had a higher ORR than patients with a variant histology component (58% vs 42%; P = .06). Conclusions In a large retrospective cohort, responses to EV monotherapy were consistent with data previously reported in clinical trials and were also observed in various patient subsets, including patients with variant histology, patients with FGFR3 alterations, and patients previously excluded from clinical trials with an estimated glomerular filtration rate < 30 mL/min and significant comorbidities. Lay Summary Enfortumab vedotin, approved by the Food and Drug Administration in 2019, is an important new drug for the treatment of patients with advanced bladder cancer. This study looks at the effectiveness of enfortumab vedotin as it has been used at multiple centers since approval, and focuses on important patient populations previously excluded from clinical trials. These populations include patients with decreased kidney function, diabetes, and important mutations. Enfortumab vedotin is effective for treating these patients. Previously reported clinical trial data have been replicated in this real‐world setting, and support the use of this drug in broader patient populations.

575 Background: Immune checkpoint inhibitors (ICI) are being increasingly utilized in front-line (1L) setting of metastatic clear-cell renal cell carcinoma (mccRCC). Limited data exist on responses and survival on second-line (2L) VEGFR-TKI therapy after 1L ICI therapy. Methods: This is a retrospective study of mccRCC patients treated with 2L VEGFR-TKI after progressive disease (PD) with 1L ICI. Patients were treated at MD Anderson Cancer Center or Memorial Sloan Kettering Cancer Center between December 2015 and February 2018. Objective response was assessed by blinded radiologists’ review using RECIST v1.1. Descriptive statistics and Kaplan-Meier method were utilized. Results: 70 patients were included in the analysis. Median age at mccRCC diagnosis was 59 years old; 8 patients (11%) had IMDC favorable-risk score, 48 (69%) had intermediate-risk score, and 14 (20%) had poor-risk score. As 1L therapy, 12 patients (17%) received anti-PD-(L)1 monotherapy with nivolumab or atezolizumab, 33 (47%) received nivolumab plus ipilimumab, and 25 (36%) received combination anti-PD-(L)1 plus bevacizumab. 2L TKI therapies included pazopanib, sunitinib, axitinib, and cabozantinib. On 2L TKI therapy, one patient (1.5%) achieved a complete remission (CR), 27 patients (39.7%) a partial response (PR), and 36 patients (52.9%) stable disease (SD), adding to a 94% disease control rate (DCR). Median progression-free survival (mPFS) was 13.2 months (95% CI: 10.1, NA). Estimated 1-yr overall survival (OS) probability was 79.6% (95% CI: 70.2 – 90.3). Median duration of 2L TKI therapy was 10.1 months. In total, 45.7% of subjects required a dose reduction, and 27% of patients discontinued treatment due to toxicity. Conclusions: In this retrospective study of patients with mccRCC receiving 2L TKI monotherapy following 1L ICI, we observed 2L antitumor activity and tolerance comparable to historical data for first-line TKI. Further studies are needed to evaluate optimal strategies and sequencing of therapies in mccRCC.

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