Background and Objective: The outcome of locally advanced and metastatic urothelial carcinoma LA/mUC has improved over the past years with a plethora of new treatments and the approval of immune checkpoint inhibitors (ICIs), antibody-drug conjugates, and targeted agents, to identify locally advanced metastatic urothelial carcinoma’s current management practices in Lebanon and the implication of the ongoing economic crisis on the medical practice. Methods: An online questionnaire was used to survey ten Lebanese oncologists from six different hospitals, between July 5 and July 11, 2022, requesting information pertaining to their current clinical practice in the pharmacological treatment of locally advanced metastatic urothelial carcinoma. Key Findings: Cisplatin-based chemotherapy was the most frequently reported initial treatment of locally advanced metastatic urothelial carcinoma. Participants reported using immune checkpoint inhibitors in platinum-ineligible patients and those with PDL1 positive tumors. Also, they would not consider the concomitant use of immunotherapy and chemotherapy in the first-line setting. Participants believed that avelumab maintenance is effective in the absence of progression after first-line platinum-based chemotherapy; they would consider initiating it 2 - 10 weeks after completion of chemotherapy. Conclusions and Clinical Implications: After comparing with current international guidelines, this study shows that Lebanese oncologists follow international guidelines and have deep knowledge of recent clinical trials for the management of locally advanced metastatic urothelial carcinoma, regardless of economic crisis challenges.
References
[1]
Sung, H., Ferlay, J., Siegel, R.L., et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249. https://doi.org/10.3322/caac.21660
[2]
Saginala, K., Barsouk, A., Aluru, J.S., et al. (2020) Epidemiology of Bladder Cancer. Medical Sciences, 8, Article No. 15. https://doi.org/10.3390/medsci8010015
[3]
Safiri, S., Kolahi, A.-A. and Naghavi, M. (2021) Global, Regional and National Burden of Bladder Cancer and Its Attributable Risk Factors in 204 Countries and Territories, 1990-2019: A Systematic Analysis for the Global Burden of Disease Study 2019. BMJ Global Health, 6, e004128. https://doi.org/10.1136/bmjgh-2020-004128
Powles, T., Bellmunt, J., Comperat, E., et al. (2022) Bladder Cancer: ESMO Clinical Practice Guideline for Diagnosis, Treatment and Follow-Up. Annals of Oncology, 33, 244-258. https://doi.org/10.1016/j.annonc.2021.11.012
[6]
Von Der Maase, H., Hansen, S.W., Roberts, J.T., et al. (2000) Gemcitabine and Cisplatin versus Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Advanced or Metastatic Bladder Cancer: Results of a Large, Randomized, Multinational, Multicenter, Phase III Study. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 18, 3068-3077. https://doi.org/10.1200/JCO.2000.18.17.3068
[7]
Von Der Maase, H., Sengelov, L., Roberts, J.T., et al. (2005) Long-Term Survival Results of a Randomized Trial Comparing Gemcitabine plus Cisplatin, with Methotrexate, Vinblastine, Doxorubicin, plus Cisplatin in Patients with Bladder Cancer. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 23, 4602-4608. https://doi.org/10.1200/JCO.2005.07.757
[8]
Lebanese Ministry of Public Health (2018) National Cancer Treatment Guidelines. https://www.moph.gov.lb/userfiles/files/quality%26safety/nationalguidelines/undp_cancerbook.pdf
[9]
Flaig, T.W., Spiess, P.E., Abern, M., et al. (2022) NCCN Guidelines® Insights: Bladder Cancer, Version 2.2022. Journal of the National Comprehensive Cancer Network, 20, 866-878.
[10]
Flaig, T.W., Spiess, P.E., Agarwal, N., et al. (2020) Bladder Cancer, Version 3.2020, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network, 18, 329-354.
[11]
Cathomas, R., Lorch, A., Bruins, H.M., et al. (2022) The 2021 Updated European Association of Urology Guidelines on Metastatic Urothelial Carcinoma. European Urology, 81, 95-103. https://doi.org/10.1016/j.eururo.2021.09.026
[12]
De Santis, M., Bellmunt, J., Mead, G., et al. (2012) Randomized Phase II/III Trial Assessing Gemcitabine/Carboplatin and Methotrexate/Carboplatin/Vinblastine in Patients with Advanced Urothelial Cancer Who Are Unfit for Cisplatin-Based Chemotherapy: EORTC Study 30986. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 30, 191-199. https://doi.org/10.1200/JCO.2011.37.3571
[13]
Balar, A.V., Galsky, M.D., Rosenberg, J.E., et al. (2017) Atezolizumab as First-Line Treatment in Cisplatin-Ineligible Patients with Locally Advanced and Metastatic Urothelial Carcinoma: A Single-Arm, Multicentre, Phase 2 Trial. The Lancet (London, England), 389, 67-76. https://doi.org/10.1016/S0140-6736(16)32455-2
[14]
Balar, A.V., Castellano, D., O’Donnell, P.H., et al. (2017) First-Line Pembrolizumab in Cisplatin-Ineligible Patients with Locally Advanced and Unresectable or Metastatic Urothelial Cancer (KEYNOTE-052): A Multicentre, Single-Arm, Phase 2 Study. The Lancet Oncology, 18, 1483-1492. https://doi.org/10.1016/S1470-2045(17)30616-2
[15]
O’Donnell, P.H., Balar, A.V., Vuky, J., et al. (2021) First-Line Pembrolizumab (Pembro) in Cisplatin-Ineligible Patients with Advanced Urothelial Cancer (UC): Response and Survival Results up to Five Years from the KEYNOTE-052 Phase 2 Study. Journal of Clinical Oncology, 39, 4508-4508. https://doi.org/10.1200/JCO.2021.39.15_suppl.4508
[16]
Galsky, M.D., Arija, J.A.A., Bamias, A., et al. (2020) Atezolizumab with or without Chemotherapy in Metastatic Urothelial Cancer (IMvigor130): A Multicentre, Randomised, Placebo-Controlled Phase 3 Trial. The Lancet (London, England), 395, 1547-1557. https://doi.org/10.1016/S0140-6736(20)30230-0
[17]
Powles, T., Csőszi, T., Özgüroğlu, M., et al. (2021) Pembrolizumab Alone or Combined with Chemotherapy versus Chemotherapy as First-Line Therapy for Advanced Urothelial Carcinoma (KEYNOTE-361): A Randomised, Open-Label, Phase 3 Trial. The Lancet Oncology, 22, 931-945.
[18]
Bellmunt, J., De Wit, R., Vaughn, D.J., et al. (2017) Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. The New England Journal of Medicine, 376, 1015-1026. https://doi.org/10.1056/NEJMoa1613683
[19]
Bellmunt, J., Théodore, C., Demkov, T., et al. (2009) Phase III Trial of Vinflunine plus Best Supportive Care Compared with Best Supportive Care Alone after a Platinum-Containing Regimen in Patients with Advanced Transitional Cell Carcinoma of the Urothelial Tract. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 27, 4454-4461. https://doi.org/10.1200/JCO.2008.20.5534
[20]
Sridhar, S.S., Blais, N., Tran, B., et al. (2020) Efficacy and Safety of Nab-Paclitaxel vs Paclitaxel on Survival in Patients with Platinum-Refractory Metastatic Urothelial Cancer: The Canadian Cancer Trials Group BL.12 Randomized Clinical Trial. JAMA Oncology, 6, 1751-1758. https://doi.org/10.1001/jamaoncol.2020.3927
[21]
FDA (2019) FDA Grants Accelerated Approval to Erdafitinib for Metastatic Urothelial Carcinoma. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-erdafitinib-metastatic-urothelial-carcinoma
[22]
Rosenberg, J.E., O’Dennell, P.H., Balar, A.V., et al. (2019) Pivotal Trial of Enfortumab Vedotin in Urothelial Carcinoma after Platinum and Anti-Programmed Death 1/Programmed Death Ligand 1 Therapy. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology, 37, Article No. 29. https://doi.org/10.1200/JCO.19.01140
[23]
Powles, T., Rosenberg, J.E., Sonpavde, G.P., et al. (2021) Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. The New England Journal of Medicine, 384, 1125-1135. https://doi.org/10.1056/NEJMoa2035807
[24]
Powles, T., Park, S.H., Voog, E., et al. (2020) Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. The New England Journal of Medicine, 383, 1218-1230. https://doi.org/10.1056/NEJMoa2002788
[25]
Sridhar, S., Powles, T.B., Loriot, Y., et al. (2020) 699O—Avelumab First-Line (1L) Maintenance + Best Supportive Care (BSC) vs BSC Alone for Advanced Urothelial Carcinoma (UC): Association between Clinical Outcomes and Exploratory Biomarkers. Annals of Oncology, 31, S550. https://oncologypro.esmo.org/meeting-resources/esmo-virtual-congress-2020/avelumab-first-line-1l-maintenance-best-supportive-care-bsc-vs-bsc-alone-for-advanced-urothelial-carcinoma-uc-association-between-clinical
[26]
World Bank (2021) Lebanon Economic Monitor, Spring 2021. In Economic Updates and Modeling.
[27]
Kattan, C. and Kattan, J. (2022) Accommodation with Anticancer Drug Shortage: A Lebanese Harmful Solution. Frontiers in Oncology, 12, Article ID: 1055113. https://doi.org/10.3389/fonc.2022.1055113
