Abstract 1759P
Background
Patients with advanced/metastatic urothelial carcinoma (a/mUC) have poor overall survival (OS) after platinum-containing chemotherapy (CTX) a/o immune-checkpoint-inhibitor (ICI) therapy. Recently, enfortumab-vedotin (EV), an antibody-drug conjugate directed against Nectin-4, was approved by EMA for UC progressing on CTX and ICI-therapy. We evaluated the the efficacy and safety of EV in routine clinical practice, predominantly prior to EMA approval.
Methods
Data were collected retrospectively from 11 tertiary cancer centres in Germany (Observation period: 11/19-04/22). Patients with a/mUC and treatment with EV were eligible (n=56). Treatments were given according to routine care, adverse events (AE) were reported according to CTCAE 5.0. Objective response rate (ORR) according to RECIST 1.1 and Progression Free Survival (PFS) were calculated from start of treatment to progression. Numerical variables are stated as median values and interquartile ranges (IQR), categorical variables with proportions %.
Results
Median age was 65 (IQR:56;72) years (76.8% male), ECOG-PS: 0-1 was present in 73.2% (n=50). Median follow-up was 4 (IQR:2;6.8) months. Prior surgery was performed in 78.6% (radical cystectomy in 51.8%). Synchronous a/mUC existed in 26.8%. Median number of therapy lines before EV initiation was 4 (IQR:3;5). ORR of EV was 28.6% (PR: 26.8%, CR: 1.8%), SD was 14.3%, and PD 23.2%, with a mixed response in 16.1%. Missing data was 17.9%. EV was given in 7.1% as 2nd, 32.1% as 3rd and 60.8% in later lines. Median treatment duration was 3 (IQR:2;5) months and PFS was 3 (IQR: 2; 5) months. At data cutoff EV therapy was ongoing in 32.1%. Discontinuation of therapy was due to PD in 44.6% and toxicity in 10.2% with documented adverse events (AE) of all grades in 78.6% and CTCAE grade ≥ 3 in 42.9%. Among those, gastrointestinal disorders (37.5%), skin reactions (35.7%) and general disorders (30.4%) were the 3 most frequent AEs of any grade and causality.
Conclusions
EV approval by EMA was based on an improved median PFS of 5.6 and median OS 12.9 months in favor of EV. In our cohort EV was safe and feasible. No new safety signals were reported. Our data support the use of EV for patients with a/mUC. Major limitations are short follow-up and retrospective study design.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Dr. med. Christopher Darr.
Funding
Has not received any funding.
Disclosure
G. Niegisch: Financial Interests, Personal, Invited Speaker: Roche Pharma, MEDAC, Pfizer, BMS, AstraZeneca; Financial Interests, Personal, Advisory Board: Sanofi, Merck, Roche Pharma, BMS, Pfizer, MEDAC, Ipsen, Janssen. P. Ivanyi: Financial Interests, Personal, Invited Speaker: Apogepha, BMS, Bayer, Böhringer Ingelheim, ClinSol, DKG-Onkoweb, Dicephera, EISAI, H5Oncology, Ipsen, Merck, MSD, Onkowissen, Pfizer, Pfizer, Roche, GSK, Pharma Mare, AstraZeneca; Financial Interests, Personal, Advisory Board: BMS, Bayer, Dicephera, EISAI, Ipsen, Merck, MSD, Onkowissen, Pfizer; Financial Interests, Personal, Expert Testimony: ClinSol, EMD Serono, Merck, Metaplan, Pfizer; Financial Interests, Personal, Stocks/Shares: BB-Biotech; Financial Interests, Institutional, Invited Speaker: BMS, AstraZeneca, GSK, Ipsen, MSD; Non-Financial Interests, Other, Spokesman: Interdisciplinary Kindey Cancer Group of German Cancer Society. N. Klümper: Financial Interests, Personal, Other, Travel costs: Novartis. B.A. Hadaschik: Financial Interests, Personal, Advisory Board: Janssen, Bayer, ABX, Lightpoint Medical, Amgen, MSD, Pfizer; Financial Interests, Institutional, Royalties: Uromed; Financial Interests, Personal and Institutional, Invited Speaker: Janssen R&D; Financial Interests, Institutional, Funding: AAA/Novartis, BMS, German Research Foundation. V. Grünwald: Financial Interests, Personal, Advisory Board: Apogepha, BMS, Debiopharm, EISAI, EUSA Pharm, Merck Serano, MSD, Nanobiotix, Oncorena, PCI Biotech, Pfizer, Roche; Financial Interests, Personal, Invited Speaker: Astellas, AstraZeneca, BMS, EISAI, Ipsen, Janssen-Cilag, Merck Serano, MSD, Novartis, Pfizer, Roche; Financial Interests, Personal, Stocks/Shares: AstraZeneca, BMS, MSD, Seattle Genetics; Financial Interests, Institutional, Research Grant: BMS, MSD; Non-Financial Interests, Personal and Institutional, Other, Steering Committee Member: BMS; Financial Interests, Personal and Institutional, Other, Steering Committee Member: EISAI, Novartis; Financial Interests, Personal and Institutional, Research Grant: IPSEN; Non-Financial Interests, Institutional, Other, Steering Committee Member: IPSEN; Non-Financial Interests, Personal, Research Grant: Pfizer; Non-Financial Interests, Personal, Other, Trial Chair: PharmaMar; Non-Financial Interests, Personal, Other, Member: ASCO, German medical Oncology and Hematology Society; Non-Financial Interests, Personal, Other, Advisory Role: German Cancer Society; Non-Financial Interests, Personal, Other, Leadership Role: Working group medical oncology. All other authors have declared no conflicts of interest.