Abstract 797TiP
Background
Patients with locally advanced bladder cancer (cT3/4 cN0/N+ cM0) have a poor prognosis despite radical surgical therapy. The addition of perioperative combination chemotherapy did not add significant benefit to surgery alone, leading to a 5-year overall survival rate < 35%. Anti-PD1/PDL1-based immunotherapies with agents like Nivolumab have shown activity in bladder cancer in the metastatic setting, leading to FDA and EMA approval in urothelial cancer. Recently, promising early data on neoadjuvant immunotherapy in muscle invasive bladder cancer was published (PURE-01, ABACUS, NABUCCO). There are preclinical and early clinical trials, which propose a synergistic effect of radiation and immunotherapy. Therefore we designed this trial to evaluate feasibility (primary endpoint), safety and efficacy (secondary endpoints) of neoadjuvant radio-immunotherapy in patients with locally advanced, muscle invasive bladder cancer.
Trial design
In this prospective, single arm, multicenter, phase II-trial, patients are treated with Nivolumab 240mg i.v. q2w for 4 cycles, starting one week before radiotherapy of the pelvis with max. 50.4 Gy. After completion of radio-immunotherapy a radical cystectomy with standardized pelvic lymphadenectomy is performed, with a postoperative follow-up phase of 1 year. Main inclusion criteria are locally advanced (cT3/4 cN0/N+ cM0) urothelial bladder cancer in patients eligible for radical cystectomy, who are unfit for neoadjuvant cisplatin-based chemotherapy or refuse neoadjuvant chemotherapy. Main exclusion criteria are metastatic disease defined as distant metastasis or suspicious lymph nodes outside the pelvis, prior chemotherapy, pelvic radiation, autoimmune disease or gastrointestinal disorders with a high risk of perforation or fistula. Since 02/2019 the trial recruited 15 patients (planned: 33 patients) and is open for recruitment. A pre-planned safety interim analysis with temporary inclusion pause was successfully performed after inclusion of 11 patients. Trial Registration: NCT03529890.
Clinical trial identification
EudraCT: 2018-001823-38, NCT03529890 Protocol Code AUO/DKG: AB 65/18.
Editorial acknowledgement
Legal entity responsible for the study
Medizinische Fakultät der Technischen Universität München, Munich, Germany.
Funding
Bristol-Myers Squibb Company.
Disclosure
S.C. Schmid: Research grant/Funding (institution), Travel/Accommodation/Expenses: Bristol Myers Squibb. A.K. Seitz: Travel/Accommodation/Expenses: Bristol Myer Squibb. P. Maisch: Travel/Accommodation/Expenses: Bristol-Myers Squibb. J. Gschwend: Advisory/Consultancy: Bristol Myer Squibb. M. Retz: Advisory/Consultancy: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.