FDA-BCAN Workshop: Endpoints for the Development of Neoadjuvant Systemic Therapy Regimens for Muscle-Invasive Bladder Cancer
August 8, 2019
- August 8, 2019
Co-sponsored by the:
U.S. Food and Drug Administration (FDA) and
the Bladder Cancer Advocacy Network (BCAN)
Thursday, August 8, 2019
12 p.m. to 4 p.m.
1001 16th Street NW
Washington, DC 20036
This workshop focuses on endpoints for the development of systemic neoadjuvant therapies for the treatment of muscle-invasive bladder cancer. Neoadjuvant cisplatin-based combination chemotherapy followed by radical cystectomy is a standard treatment for muscle-invasive urothelial cancer of the bladder. However, the current treatment paradigm has several limitations:
- Neoadjuvant cisplatin-based chemotherapy is associated with a modest to moderate improvement in survival and the data to support its use is decades old without any updated regimens that have demonstrated improvement in outcomes.
- Approximately 30-40% of patients treated with neoadjuvant cisplatin-based chemotherapy achieve a pathologic complete response. Pathologic complete response has been correlated with improved survival in patients treated with neoadjuvant chemotherapy, raising the possibility for its use as an intermediate endpoint to accelerate the development of novel neoadjuvant regimens. The potential role of pathologic complete response as an individual- and trial-level surrogate endpoint in this disease is poorly defined.
- A large subset of patients with muscle-invasive bladder cancer are “cisplatin-ineligible,” predominantly due to renal impairment. For such patients, there are no standard perioperative systemic therapy approaches available.
- Given concerns regarding the potential for clinical-pathologic stage discrepancies, documenting a pathologic complete response has historically been achievable only after patients have undergone life-altering surgery (i.e., given the need for urinary diversion). The potential for achieving a pathologic complete response raises the possibility of a paradigm-shifting approach of curative-intent systemic therapy alone in a subset of patients with muscle-invasive urothelial cancer of the bladder. The examinations required to adequately document a clinical complete response, and the definition of clinical complete response have not been standardized. This precludes an adequate understanding of the relationship between clinical complete response, pathologic complete response, and long-term outcomes.
- Provide a forum for open discussion between clinicians, regulatory scientists, biostatisticians, patients, advocates, and industry representatives regarding the role of pathologic complete response rate as an endpoint to accelerate the development of novel neoadjuvant systemic therapies for the treatment of muscle-invasive bladder cancer.
- Obtain input from multiple stakeholders on approaches to document clinical complete response with neoadjuvant systemic therapy for the treatment of muscle-invasive bladder cancer, to elucidate the clinical relevance of clinical complete response to advance a potential therapeutic strategy of using systemic therapy alone as a curative-intent approach to the treatment of muscle-invasive bladder cancer.
- Map out priorities for further evidence development to address knowledge gaps.
FDA archived webcast of this meeting is available as follows:
Stephanie Chisolm, PhD
Director of Education and Research
Frank Cross, Jr.
|FDA-BCANFnalAgenda||pdf (174.68 KB)|