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Chang E , Apolo AB , Bangs R , Chisolm S , Duddalwar V , Efstathiou JA , Goldberg KB , Hansel DE , Kamat AM , Kluetz PG , Lerner SP , Plimack E , Prowell T , Singh H , Suzman D , Yu EY , Zhang H , Beaver JA , Pazdur R , Weinstock C , Galsky MD
Refining neoadjuvant therapy clinical trial design for muscle-invasive bladder cancer before cystectomy: a joint US Food and Drug Administration and Bladder Cancer Advocacy Network workshop
Nat Rev Urol. 2021 Sep 10
PMID: 34508246   
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Abstract
The success of the use of novel therapies in the treatment of advanced urothelial carcinoma has contributed to growing interest in evaluating these therapies at earlier stages of the disease. However, trials evaluating these therapies in the neoadjuvant setting must have clearly defined study elements and appropriately selected end points to ensure the applicability of the trial and enable interpretation of the study results. To advance the development of rational trial design, a public workshop jointly sponsored by the US Food and Drug Administration and the Bladder Cancer Advocacy Network convened in August 2019. Clinicians, clinical trialists, radiologists, biostatisticians, patients, advocates and other stakeholders discussed key elements and end points when designing trials of neoadjuvant therapy for muscle-invasive bladder cancer (MIBC), identifying opportunities to refine eligibility, design and end points for neoadjuvant trials in MIBC. Although pathological complete response (pCR) is already being used as a co-primary end point, both individual-level and trial-level surrogacy for time-to-event end points, such as event-free survival or overall survival, remain incompletely characterized in MIBC. Additionally, use of pCR is limited by heterogeneity in pathological evaluation and the fact that the magnitude of pCR improvement that might translate into a meaningful clinical benefit remains unclear. Given existing knowledge gaps, capture of highly granular patient-related, tumour-related and treatment-related characteristics in the current generation of neoadjuvant MIBC trials will be critical to informing the design of future trials.
Notes
1759-4820 Chang, Elaine Orcid: 0000-0001-6255-2853 Apolo, Andrea B Orcid: 0000-0001-9409-1836 Bangs, Rick Orcid: 0000-0002-0706-8775 Chisolm, Stephanie Orcid: 0000-0002-6194-3163 Duddalwar, Vinay Orcid: 0000-0002-4808-5715 Efstathiou, Jason A Goldberg, Kirsten B Orcid: 0000-0001-8659-1240 Hansel, Donna E Orcid: 0000-0001-7860-4881 Kamat, Ashish M Orcid: 0000-0003-3546-9928 Kluetz, Paul G Lerner, Seth P Plimack, Elizabeth Prowell, Tatiana Singh, Harpreet Suzman, Daniel Yu, Evan Y Zhang, Hui Beaver, Julia A Pazdur, Richard Weinstock, Chana Galsky, Matthew D Journal Article Review England Nat Rev Urol. 2021 Sep 10. doi: 10.1038/s41585-021-00505-w.