Revisiting Treatment of Metastatic Urothelial Cancer: Where Do Cisplatin and Platinum Ineligibility Criteria Stand?
Cisplatin-based chemotherapy has been the standard of care in metastatic urothelial cancer (mUC) for more than two decades. However, many patients with comorbidities cannot receive cisplatin or its alternative, carboplatin. ‘Cisplatin-ineligible’ and ‘platinum-ineligible’ patients lacked effective t...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/12/3/519 |
| _version_ | 1827306946305196032 |
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| author | Mohammad Jad Moussa Matthew T. Campbell Omar Alhalabi |
| author_facet | Mohammad Jad Moussa Matthew T. Campbell Omar Alhalabi |
| author_sort | Mohammad Jad Moussa |
| collection | DOAJ |
| description | Cisplatin-based chemotherapy has been the standard of care in metastatic urothelial cancer (mUC) for more than two decades. However, many patients with comorbidities cannot receive cisplatin or its alternative, carboplatin. ‘Cisplatin-ineligible’ and ‘platinum-ineligible’ patients lacked effective therapy options. However, the recent combination of enfortumab vedotin (EV), an antibody–drug conjugate targeting Nectin-4, with pembrolizumab (P), an antibody targeting the programmed death-1 (PD-1) immune checkpoint, is changing the status quo of frontline mUC treatment, with potential synergy seen in the EV-103 and EV-302 clinical trials. First, we review the working definitions of ‘cisplatin ineligibility’ and ‘platinum ineligibility’ in mUC clinical trials and the standard of care in both categories. Then, we review select clinical trials for frontline treatment of cisplatin- and platinum-ineligible mUC patients on ClinicalTrials.gov. We classify the investigated drugs in these trials by their therapeutic strategies. Alongside chemotherapy combinations, the field is witnessing more immunotherapy combinations with fibroblast growth factor receptor (FGFR) inhibitors, bicycle toxin conjugates, bispecific antibodies, innovative targeted therapies, and many others. Most importantly, we rethink the value of classifying patients by cisplatin or platinum ineligibility in the frontline setting in the post-EVP era. Lastly, we discuss new priority goals to tailor predictive, monitoring, and prognostic biomarkers to these emergent therapies. |
| first_indexed | 2024-04-24T18:32:07Z |
| format | Article |
| id | doaj.art-377a74046c09489887e9cdd18dbe7230 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-04-24T18:32:07Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-377a74046c09489887e9cdd18dbe72302024-03-27T13:22:39ZengMDPI AGBiomedicines2227-90592024-02-0112351910.3390/biomedicines12030519Revisiting Treatment of Metastatic Urothelial Cancer: Where Do Cisplatin and Platinum Ineligibility Criteria Stand?Mohammad Jad Moussa0Matthew T. Campbell1Omar Alhalabi2Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USACisplatin-based chemotherapy has been the standard of care in metastatic urothelial cancer (mUC) for more than two decades. However, many patients with comorbidities cannot receive cisplatin or its alternative, carboplatin. ‘Cisplatin-ineligible’ and ‘platinum-ineligible’ patients lacked effective therapy options. However, the recent combination of enfortumab vedotin (EV), an antibody–drug conjugate targeting Nectin-4, with pembrolizumab (P), an antibody targeting the programmed death-1 (PD-1) immune checkpoint, is changing the status quo of frontline mUC treatment, with potential synergy seen in the EV-103 and EV-302 clinical trials. First, we review the working definitions of ‘cisplatin ineligibility’ and ‘platinum ineligibility’ in mUC clinical trials and the standard of care in both categories. Then, we review select clinical trials for frontline treatment of cisplatin- and platinum-ineligible mUC patients on ClinicalTrials.gov. We classify the investigated drugs in these trials by their therapeutic strategies. Alongside chemotherapy combinations, the field is witnessing more immunotherapy combinations with fibroblast growth factor receptor (FGFR) inhibitors, bicycle toxin conjugates, bispecific antibodies, innovative targeted therapies, and many others. Most importantly, we rethink the value of classifying patients by cisplatin or platinum ineligibility in the frontline setting in the post-EVP era. Lastly, we discuss new priority goals to tailor predictive, monitoring, and prognostic biomarkers to these emergent therapies.https://www.mdpi.com/2227-9059/12/3/519metastatic urothelial cancercisplatin-based chemotherapyplatinum-based chemotherapycisplatin ineligibleplatinum ineligibleenfortumab vedotin |
| spellingShingle | Mohammad Jad Moussa Matthew T. Campbell Omar Alhalabi Revisiting Treatment of Metastatic Urothelial Cancer: Where Do Cisplatin and Platinum Ineligibility Criteria Stand? Biomedicines metastatic urothelial cancer cisplatin-based chemotherapy platinum-based chemotherapy cisplatin ineligible platinum ineligible enfortumab vedotin |
| title | Revisiting Treatment of Metastatic Urothelial Cancer: Where Do Cisplatin and Platinum Ineligibility Criteria Stand? |
| title_full | Revisiting Treatment of Metastatic Urothelial Cancer: Where Do Cisplatin and Platinum Ineligibility Criteria Stand? |
| title_fullStr | Revisiting Treatment of Metastatic Urothelial Cancer: Where Do Cisplatin and Platinum Ineligibility Criteria Stand? |
| title_full_unstemmed | Revisiting Treatment of Metastatic Urothelial Cancer: Where Do Cisplatin and Platinum Ineligibility Criteria Stand? |
| title_short | Revisiting Treatment of Metastatic Urothelial Cancer: Where Do Cisplatin and Platinum Ineligibility Criteria Stand? |
| title_sort | revisiting treatment of metastatic urothelial cancer where do cisplatin and platinum ineligibility criteria stand |
| topic | metastatic urothelial cancer cisplatin-based chemotherapy platinum-based chemotherapy cisplatin ineligible platinum ineligible enfortumab vedotin |
| url | https://www.mdpi.com/2227-9059/12/3/519 |
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