Cargando…
Enfortumab Vedotin in Metastatic Urothelial Carcinoma: Survival and Safety in a European Multicenter Real-world Patient Cohort
BACKGROUND: Treatment options for patients with urothelial cancer (UC) refractory to platinum and immunotherapy are limited and survival is short. Enfortumab vedotin (EV) is a monoclonal anti-NECTIN4 antibody conjugated to monomethyl auristatin. It was recently approved because of superior survival...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10334227/ https://www.ncbi.nlm.nih.gov/pubmed/37441344 http://dx.doi.org/10.1016/j.euros.2023.04.018 |
_version_ | 1785070817074216960 |
---|---|
author | Zschäbitz, Stefanie Biernath, Nadine Hilser, Thomas Höllein, Alexander Zengerling, Friedemann Cascucelli, Jozefina Paffenholz, Pia Seidl, Daniel Lutz, Christoph Schlack, Katrin Kingreen, Dorothea Klümper, Niklas Ivanyi, Philipp von Amsberg, Gunhild Heers, Hendrik Roghmann, Florian Tauber, Robert L. Cathomas, Richard Hofer, Luisa Niegisch, Günter Klee, Melanie Ehrenberg, Roland Hassler, Andreas Hadaschik, Boris A. Grünwald, Viktor Darr, Christopher |
author_facet | Zschäbitz, Stefanie Biernath, Nadine Hilser, Thomas Höllein, Alexander Zengerling, Friedemann Cascucelli, Jozefina Paffenholz, Pia Seidl, Daniel Lutz, Christoph Schlack, Katrin Kingreen, Dorothea Klümper, Niklas Ivanyi, Philipp von Amsberg, Gunhild Heers, Hendrik Roghmann, Florian Tauber, Robert L. Cathomas, Richard Hofer, Luisa Niegisch, Günter Klee, Melanie Ehrenberg, Roland Hassler, Andreas Hadaschik, Boris A. Grünwald, Viktor Darr, Christopher |
author_sort | Zschäbitz, Stefanie |
collection | PubMed |
description | BACKGROUND: Treatment options for patients with urothelial cancer (UC) refractory to platinum and immunotherapy are limited and survival is short. Enfortumab vedotin (EV) is a monoclonal anti-NECTIN4 antibody conjugated to monomethyl auristatin. It was recently approved because of superior survival in comparison to standard-of-care (SOC) chemotherapy. Real-world patients, however, often have worse characteristics than patients included in clinical trials. OBJECTIVE: To analyze the efficacy and safety of EV in a cohort of real-world patients. DESIGN, SETTING, AND PARTICIPANTS: Retrospective data were collected from 23 hospitals and private practices for patients with metastatic and previously treated UC who received EV either when reimbursed by their insurance company before European Medicines Agency (EMA) approval, within a compassionate use program, or as SOC treatment after EMA approval. Imaging and therapy management were in accordance with local standards. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Adverse events (AEs) were reported according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Objective responses were evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS AND LIMITATIONS: The median age for the 125 eligible patients was 66 yr (range 31–89). The Eastern Cooperative Oncology Group performance status (ECOG PS) was 0–1 for 76.0%, 2–4 for 13.6%, and unknown for 10.4% of patients. EV was administered in the fourth or later line for 44.8% of patients. The overall response rate was 41.6% (partial response 39.2%, complete response 2.4%). Median OS was 10.0 months (mo) (95% confidence interval 7.20–12.80) and median PFS was 5.0 mo (95% confidence interval 4.34–5.67). For patients with ECOG PS of 0–1, median OS was 14 mo. Any-grade AEs were observed in 67.2% and CTCAE grade ≥3 AEs in 30.4%. The most common AEs were peripheral sensory neuropathy and skin toxicity. Three fatal events (pneumonia, pneumonitis) occurred. Limitations include the retrospective design and short follow-up. CONCLUSIONS: Administration of EV for real-world patients was feasible with an acceptable toxicity profile. No new safety signals were reported. Antitumor activity in our cohort was comparable to data previously reported for trials. In summary, our results support the use of EV in patients with metastatic UC. PATIENT SUMMARY: Enfortumab vedotin is a medication that improved the survival of patients with bladder cancer in comparison to standard chemotherapy in clinical trials. However, patients included in clinical trials are highly selected and results for toxicities and improvements in survival do not always transfer to the real-world setting. We analyzed data for 125 patients who were treated with enfortumab vedotin. Our results are comparable to the outcomes from clinical trials regarding the safety and efficacy of this treatment. |
format | Online Article Text |
id | pubmed-10334227 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-103342272023-07-12 Enfortumab Vedotin in Metastatic Urothelial Carcinoma: Survival and Safety in a European Multicenter Real-world Patient Cohort Zschäbitz, Stefanie Biernath, Nadine Hilser, Thomas Höllein, Alexander Zengerling, Friedemann Cascucelli, Jozefina Paffenholz, Pia Seidl, Daniel Lutz, Christoph Schlack, Katrin Kingreen, Dorothea Klümper, Niklas Ivanyi, Philipp von Amsberg, Gunhild Heers, Hendrik Roghmann, Florian Tauber, Robert L. Cathomas, Richard Hofer, Luisa Niegisch, Günter Klee, Melanie Ehrenberg, Roland Hassler, Andreas Hadaschik, Boris A. Grünwald, Viktor Darr, Christopher Eur Urol Open Sci Urothelial Cancer BACKGROUND: Treatment options for patients with urothelial cancer (UC) refractory to platinum and immunotherapy are limited and survival is short. Enfortumab vedotin (EV) is a monoclonal anti-NECTIN4 antibody conjugated to monomethyl auristatin. It was recently approved because of superior survival in comparison to standard-of-care (SOC) chemotherapy. Real-world patients, however, often have worse characteristics than patients included in clinical trials. OBJECTIVE: To analyze the efficacy and safety of EV in a cohort of real-world patients. DESIGN, SETTING, AND PARTICIPANTS: Retrospective data were collected from 23 hospitals and private practices for patients with metastatic and previously treated UC who received EV either when reimbursed by their insurance company before European Medicines Agency (EMA) approval, within a compassionate use program, or as SOC treatment after EMA approval. Imaging and therapy management were in accordance with local standards. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Adverse events (AEs) were reported according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 criteria. Objective responses were evaluated according to Response Evaluation Criteria in Solid Tumors version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS AND LIMITATIONS: The median age for the 125 eligible patients was 66 yr (range 31–89). The Eastern Cooperative Oncology Group performance status (ECOG PS) was 0–1 for 76.0%, 2–4 for 13.6%, and unknown for 10.4% of patients. EV was administered in the fourth or later line for 44.8% of patients. The overall response rate was 41.6% (partial response 39.2%, complete response 2.4%). Median OS was 10.0 months (mo) (95% confidence interval 7.20–12.80) and median PFS was 5.0 mo (95% confidence interval 4.34–5.67). For patients with ECOG PS of 0–1, median OS was 14 mo. Any-grade AEs were observed in 67.2% and CTCAE grade ≥3 AEs in 30.4%. The most common AEs were peripheral sensory neuropathy and skin toxicity. Three fatal events (pneumonia, pneumonitis) occurred. Limitations include the retrospective design and short follow-up. CONCLUSIONS: Administration of EV for real-world patients was feasible with an acceptable toxicity profile. No new safety signals were reported. Antitumor activity in our cohort was comparable to data previously reported for trials. In summary, our results support the use of EV in patients with metastatic UC. PATIENT SUMMARY: Enfortumab vedotin is a medication that improved the survival of patients with bladder cancer in comparison to standard chemotherapy in clinical trials. However, patients included in clinical trials are highly selected and results for toxicities and improvements in survival do not always transfer to the real-world setting. We analyzed data for 125 patients who were treated with enfortumab vedotin. Our results are comparable to the outcomes from clinical trials regarding the safety and efficacy of this treatment. Elsevier 2023-05-17 /pmc/articles/PMC10334227/ /pubmed/37441344 http://dx.doi.org/10.1016/j.euros.2023.04.018 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Urothelial Cancer Zschäbitz, Stefanie Biernath, Nadine Hilser, Thomas Höllein, Alexander Zengerling, Friedemann Cascucelli, Jozefina Paffenholz, Pia Seidl, Daniel Lutz, Christoph Schlack, Katrin Kingreen, Dorothea Klümper, Niklas Ivanyi, Philipp von Amsberg, Gunhild Heers, Hendrik Roghmann, Florian Tauber, Robert L. Cathomas, Richard Hofer, Luisa Niegisch, Günter Klee, Melanie Ehrenberg, Roland Hassler, Andreas Hadaschik, Boris A. Grünwald, Viktor Darr, Christopher Enfortumab Vedotin in Metastatic Urothelial Carcinoma: Survival and Safety in a European Multicenter Real-world Patient Cohort |
title | Enfortumab Vedotin in Metastatic Urothelial Carcinoma: Survival and Safety in a European Multicenter Real-world Patient Cohort |
title_full | Enfortumab Vedotin in Metastatic Urothelial Carcinoma: Survival and Safety in a European Multicenter Real-world Patient Cohort |
title_fullStr | Enfortumab Vedotin in Metastatic Urothelial Carcinoma: Survival and Safety in a European Multicenter Real-world Patient Cohort |
title_full_unstemmed | Enfortumab Vedotin in Metastatic Urothelial Carcinoma: Survival and Safety in a European Multicenter Real-world Patient Cohort |
title_short | Enfortumab Vedotin in Metastatic Urothelial Carcinoma: Survival and Safety in a European Multicenter Real-world Patient Cohort |
title_sort | enfortumab vedotin in metastatic urothelial carcinoma: survival and safety in a european multicenter real-world patient cohort |
topic | Urothelial Cancer |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10334227/ https://www.ncbi.nlm.nih.gov/pubmed/37441344 http://dx.doi.org/10.1016/j.euros.2023.04.018 |
work_keys_str_mv | AT zschabitzstefanie enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT biernathnadine enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT hilserthomas enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT holleinalexander enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT zengerlingfriedemann enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT cascucellijozefina enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT paffenholzpia enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT seidldaniel enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT lutzchristoph enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT schlackkatrin enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT kingreendorothea enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT klumperniklas enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT ivanyiphilipp enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT vonamsberggunhild enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT heershendrik enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT roghmannflorian enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT tauberrobertl enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT cathomasrichard enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT hoferluisa enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT niegischgunter enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT kleemelanie enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT ehrenbergroland enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT hasslerandreas enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT hadaschikborisa enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT grunwaldviktor enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort AT darrchristopher enfortumabvedotininmetastaticurothelialcarcinomasurvivalandsafetyinaeuropeanmulticenterrealworldpatientcohort |