Unequal Access to Novel Systemic Therapies for Bladder Cancer: A Global Analysis of Clinical Trials of Immune Checkpoint Inhibitors and Antibody-Drug Conjugates

Balar AV, Castellano DE, Grivas P, Vaughn DJ, Powles T, Vuky J, et al. Efficacy and safety of pembrolizumab in metastatic urothelial carcinoma: results from KEYNOTE-045 and KEYNOTE-052 after up to 5 years of follow-up. Ann Oncol. 2023;34(3):289–99.

Article  CAS  PubMed  Google Scholar 

Powles T, Csőszi T, Özgüroğlu M, Matsubara N, Géczi L, Cheng SYS, et al. 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. Lancet Oncol. 2021;22(7):931–45.

Article  CAS  PubMed  Google Scholar 

Powles T, Rosenberg JE, Sonpavde GP, Loriot Y, Durán I, Lee JL, et al. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma. N Engl J Med. 2021;384(12):1125–35.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tagawa ST, Balar AV, Petrylak DP, Kalebasty AR, Loriot Y, Fléchon A, et al. TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors. J Clin Oncol. 2021;39(22):2474–85.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hoimes CJ, Flaig TW, Milowsky MI, Friedlander TW, Bilen MA, Gupta S, et al. Enfortumab Vedotin Plus Pembrolizumab in Previously Untreated Advanced Urothelial Cancer. J Clin Oncol. 2023;41(1):22–31.

Article  CAS  PubMed  Google Scholar 

O’Donnell PH, Milowsky MI, Petrylak DP, Hoimes CJ, Flaig TW, Mar N et al. Enfortumab Vedotin With or Without Pembrolizumab in Cisplatin-Ineligible Patients With Previously Untreated Locally Advanced or Metastatic Urothelial Cancer. J Clin Oncol. 2023.

Galsky MD, Arija JÁA, Bamias A, Davis ID, De Santis M, Kikuchi E, et al. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020;395(10236):1547–57.

Article  CAS  PubMed  Google Scholar 

Wang L, Shi G, Zhao G, He W, Cen Z, Xu F. Efficacy and safety of enfortumab vedotin in the treatment of advanced urothelial carcinoma: a systematic review and meta-analysis. Anticancer Drugs. 2023;34(4):473–8.

Article  CAS  PubMed  Google Scholar 

Alt M, Stecca C, Tobin S, Jiang DM, Sridhar SS. Enfortumab Vedotin in urothelial cancer. Ther Adv Urol. 2020;12:175628722098019.

Article  Google Scholar 

Chin K, Chand VK, Nuyten DSA. Avelumab: clinical trial innovation and collaboration to advance anti-PD-L1 immunotherapy. Ann Oncol. 2017;28(7):1658–66.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kamat AM, Steinberg GD, Inman BA, Kates MR, Uchio EM, Porten SP, et al. Study EV-104: Phase 1 study of intravesical Enfortumab Vedotin for treatment of patients with non-muscle invasive bladder cancer (NMIBC)—Trial in progress. J Clin Oncol. 2023;41(6suppl):TPS582–582.

Article  Google Scholar 

Flaig TW, Rosenberg JE, Hoimes CJ, O’Donnell PH, Mar N, Gourdin TS, et al. Study EV-103: Neoadjuvant treatment with Enfortumab Vedotin monotherapy in cisplatin-ineligible patients (pts) with muscle invasive bladder cancer (MIBC): Updated results for Cohort H. J Clin Oncol. 2023;41(16suppl):4595–4595.

Article  Google Scholar 

Magee DE, Hird AE, Klaassen Z, Sridhar SS, Nam RK, Wallis CJD, et al. Adverse event profile for immunotherapy agents compared with chemotherapy in solid organ tumors: a systematic review and meta-analysis of randomized clinical trials. Ann Oncol. 2020;31(1):50–60.

Article  CAS  PubMed  Google Scholar 

Maisch P, Hwang EC, Kim K, Narayan VM, Bakker C, Kunath F, et al. Immunotherapy for advanced or metastatic urothelial carcinoma. Cochrane Database Syst Reviews. 2023;2023:10.

Google Scholar 

World Bank Country and Lending Groups. – World Bank Data Help Desk [Internet]. Available: https://datahelpdesk.worldbank.org/knowledgebase/articles/906519-world-bank-country-and-lending-groups

Johnson DB, Nebhan CA, Moslehi JJ, Balko JM. Immune-checkpoint inhibitors: long-term implications of toxicity. Nat Rev Clin Oncol. 2022;19(4):254–67.

Article  PubMed  PubMed Central  Google Scholar 

Shastry M, Gupta A, Chandarlapaty S, Young M, Powles T, Hamilton E. Rise of Antibody-Drug Conjugates: The Present and Future. American Society of Clinical Oncology Educational Book; 2023. (43).

Avellini C, Licini C, Lazzarini R, Gesuita R, Guerra E, Tossetta G, et al. The trophoblast cell surface antigen 2 and miR-125b axis in urothelial bladder cancer. Oncotarget. 2017;8(35):58642–53.

Article  PubMed  PubMed Central  Google Scholar 

Powles T, Valderrama BP, Gupta S, et al. Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer. N Engl J Med. 2024;390:875–88.

Article  CAS  PubMed  Google Scholar 

Powles TB, Van der Heijden MS, Loriot Y, et al. Enfortumab vedotin plus pembrolizumab in untreated locally advanced or metastatic urothelial carcinoma: 2.5-year median follow-up of the phase III EV-302/KEYNOTE-A39 trial. Ann Oncol. 2025;36(10):1212–9.

Article  CAS  PubMed  Google Scholar 

Jain P, Naqvi SAA, Tripathi N, et al. Real-World Outcomes of Enfortumab Vedotin and Pembrolizumab in Advanced Urothelial Carcinoma: A Multicenter Retrospective Analysis. Clin Genitourin Cancer. 2025;23(6):102453.

Article  PubMed  Google Scholar 

Galsky MD, Powles T, Balar AV, Sonpavde G, Gupta S, Bellmunt J, et al. Nivolumab plus Gemcitabine and Cisplatin in Advanced Urothelial Carcinoma. N Engl J Med. 2024;390(4):321–33.

Google Scholar 

Steinberg GD, Shore ND, Palou Redorta J, Galsky MD, Bedke J, Ku JH, et al. CREST: phase III study of sasanlimab and Bacillus Calmette-Guérin for patients with Bacillus Calmette-Guérin-naïve high-risk non-muscle-invasive bladder cancer. Future Oncol. 2024;20(9):891–901.

Article  CAS  PubMed  Google Scholar 

Alemayehu C, Mitchell G, Nikles J. Barriers for conducting clinical trials in developing countries—a systematic review. Int J Equity Health. 2018;17(1):37.

Article  PubMed  PubMed Central  Google Scholar 

Costello A, Zumla A. Moving to research partnerships in developing countries. BMJ. 2000;321(7264):827–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lang T, Siribaddana S. Clinical trials have gone global: is this a good thing? PLoS Med. 2012;9(6):e1001228.

Article  PubMed  PubMed Central  Google Scholar 

Gyawali B, Sullivan R. Economic evaluation of cancer medicines: missing the woods for the trees. Nat Rev Clin Oncol. 2017;14(11):693–700.

Google Scholar 

Pramesh CS, Badwe RA, Bhoo-Pathy N, et al. Cancer care and research in low- and middle-income countries: a critical review of the current situation and opportunities for improvement. Lancet Oncol. 2022;23(6):e280–92.

Google Scholar 

World Health Organization. Global Report on Effective Access to Health Products 2023. Geneva: WHO; 2023.

Google Scholar 

Rubagumya F, Hopman WM, Gyawali B, et al. Participation of lower- and upper-middle–income countries in oncology clinical trials led by high-income countries. JAMA Netw Open. 2022;5(8):e2227252.

Article  PubMed  PubMed Central  Google Scholar 

Booth CM, Karim S, Mackillop WJ. Real-world data: towards achieving the achievable in cancer care. Nat Rev Clin Oncol. 2019;16(5):312–25.

Article  PubMed  Google Scholar 

Emanuel EJ, Wendler D, Killen J, Grady C. What makes clinical research in developing countries ethical? J Infect Dis. 2004;189(5):930–7.

Article  PubMed  Google Scholar 

Hyder AA, Merritt MW, Ali J, et al. Integrating ethics, equity, and social value in global health research. Lancet. 2014;383(9919):1415–6.

Google Scholar 

Gyawali B, Sullivan R. Global access to cancer medicines: moving beyond the 90 − 10 gap. J Glob Oncol. 2017;3(2):156–8.

Google Scholar 

Chen Z, Zhong H, Hu HX et al. Chinese innovative drug R&D trends in 2024. Nat Rev Drug Discov. 2024, 0731 (2024).

Tang L. Analysis of China-to-West pharmaceutical licensing deals in 2024. Nat Rev Drug Discov. 2025;24(6):411–2.

Article  CAS  PubMed  Google Scholar 

Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12–49.

PubMed  Google Scholar 

Flaig TW, Spiess PE, Abern M, Agarwal N, Bangs R, Boorjian SA, et al. NCCN Guidelines® Insights: Bladder Cancer, Version 2.2022. J Natl Compr Canc Netw. 2022;20(8):866–78.

Article  PubMed  Google Scholar 

Hoimes CJ, Adra N, Fleming MT, Kaimakliot

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