Abstract 771P
Background
Enfortumab vedotin (EV) is an antibody-drug conjugate with activity across multiple treatment settings in advanced urothelial carcinoma (aUC) that recently received FDA approval in treatment-refractory aUC. As real-world use of this agent grows, it is important to define activity in patient (pt) subsets of interest.
Methods
Retrospective review of aUC pts treated with ≥1 dose of EV was undertaken across 8 US sites. Pts receiving EV on a clinical trial (if reported) and as standard of care (SOC) were included. ORR was assessed by investigator at each site for all pts with at least one post-baseline scan or evidence of clinical PD following EV start.
Results
Among 83 pts, median age was 68.5 years, 23% were women, primary site was bladder (70%) or upper tract (29%); 66% had definitive surgery. Most pts (74%) had pure urothelial histology (UH), but 26% had variant histology (VH), mostly squamous (10%) or micropapillary (7%). In the metastatic (met) setting, 65% had ≥ 1 and 20% ≥ 3 treatment lines prior to EV. EV was given as monotherapy to 69% and as SOC for 43%. At EV start, ECOG PS was ≥2 in 13%; 29% had baseline neuropathy, 16% diabetes, 6% had GFR≤30 and 59% GFR≤60. Median time from met diagnosis to EV start was 122 (IQR: 56 - 246) wks. After median follow-up of 32 (IQR: 10-91) wks following EV start, median duration of EV treatment was 12 (IQR: 4 - 26) wks and 77% of pts were response evaluable. ORR was 47% (8% CR, 39% PR); 16% had SD and 14% PD as best response; 23% were not yet evaluable (mostly SOC pts). At data cutoff, 54% had stopped EV (27% due to PD, 21% intolerance) and 65% were alive. ORRs in subgroups of interest are shown in the table. Adverse events (AEs) of any grade due to EV occurred in 82%, most commonly fatigue (18%), rash (14%), neuropathy (12%), and 25% had ≥G3 AEs (1 pt with G5 event). Table: 771P
| Subset | N | ORR (%, 95% CI) |
| SOC Clinical Trial | 36 47 | 22 (12, 38) 66 (52, 78) |
| Monotherapy Combination | 57 26 | 40 (29, 53) 62 (43, 78) |
| UH VH | 61 22 | 48 (36, 60) 45 (27, 65) |
| Bladder Upper Tract | 58 24 | 48 (36, 61) 46 (28, 65) |
| Liver Mets No Liver Mets | 26 57 | 42 (26, 61) 49 (37, 62) |
| ECOG PS 0/1 ECOG PS 2/3 | 72 11 | 50 (39, 61) 27 (10, 57) |
| BL Neuropathy | 24 | 58 (39, 76) |
| BL Diabetes | 13 | 31 (13, 58) |
| GFR ≤ 30 GFR 30-60 GFR > 60 | 6 43 34 | 50 (19, 81) 47 (33, 61) 47 (31, 63) |
| FGFR3 Altered | 7 | 14 (1, 51) |
Conclusions
EV has clinical efficacy across a broad spectrum of pts with aUC, including subsets not represented in clinical trials. Comparisons among the populations of interest are warranted and require longer follow-up.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
V.S. Koshkin: Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Advisory/Consultancy: AstraZeneca; Speaker Bureau/Expert testimony: Astellas / Seattle Genetics; Advisory/Consultancy: Dendreon; Research grant/Funding (institution): Nektar; Research grant/Funding (institution): Endocyte; Research grant/Funding (institution): Clovis. A.R. Khaki: Shareholder/Stockholder/Stock options: Pfizer; Shareholder/Stockholder/Stock options: Procter & Gamble. A. Basu: Travel/Accommodation/Expenses: DAVAOncology. P.M. Coelho Barata: Advisory/Consultancy: Bayer; Advisory/Consultancy: BMS; Advisory/Consultancy: Caris; Advisory/Consultancy: Eisai; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Pfizer; Honoraria (institution): Clovis; Honoraria (institution): Dendreon; Research grant/Funding (institution): Blueearth. N. Davis: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Calithera Biosciences; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Hoffman-LaRoche; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Jounce Therapeutics; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Mirati; Research grant/Funding (institution): Seattle Genetics. P. Grivas: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: BMS; Advisory/Consultancy: Bayer; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: EMD Serono; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Janssen; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: QED Therapeutics; Research grant/Funding (institution): Bavarian Nordic; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Clovis Oncology; Research grant/Funding (institution): Immunomedics; Research grant/Funding (institution): Pfizer. M. Milowsky: Advisory/Consultancy: BioClin Therapeutics; Research grant/Funding (institution): Astellas; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Clovis Oncology; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Inovio; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Seattle Genetics. D. Kilari: Advisory/Consultancy: Exelixis; Advisory/Consultancy: Sanofi; Speaker Bureau/Expert testimony: Janssen; Speaker Bureau/Expert testimony: Genzyme; Speaker Bureau/Expert testimony: Exelixis; Research grant/Funding (institution): Astellas; Travel/Accommodation/Expenses: Exelixis. A. Alva: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: BMS; Advisory/Consultancy, Travel/Accommodation/Expenses: Merck; Advisory/Consultancy: Pfizer; Research grant/Funding (institution): Arcus; Research grant/Funding (institution): Astellas; Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Harpoon; Research grant/Funding (institution): Janssen; Research grant/Funding (institution): Prometheus; Research grant/Funding (self): Roche. All other authors have declared no conflicts of interest.