Abstract
IntroductionCisplatin-based neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for patients with non-metastatic muscle invasive bladder cancer (MIBC). Unfortunately, many patients are not candidates to receive cisplatin due to renal impairment. Additionally, no predictive biomarkers for pathological complete response (pCR) are currently validated in clinical practice. Studies evaluating immune checkpoint inhibitors in the peri-operative setting are emerging with promising results. Clinical trials are clearly required in the neoadjuvant setting in order to improve therapeutic strategies.Methods and analysisOncodistinct 004 – AURA is an ongoing multicenter phase II randomized trial assessing the efficacy and safety of avelumab single-agent or combined to different NAC regimens in patients with non-metastatic MIBC. Patients are enrolled in two distinct cohorts according to their eligibility to receive cisplatin-based NAC. In the cisplatin eligible cohort, patients are randomized in a 1:1 fashion to receive avelumab combined with cisplatin-gemcitabine or with dose-dense methotrexate-vinblastine-doxorubicin-cisplatin. In the cisplatin ineligible cohort, patients are randomized at a 1:1 ratio to paclitaxel-gemcitabine associated to avelumab or avelumab alone. Primary endpoint is pCR. Secondary endpoints are pathological response and safety.Ethics and disseminationThe study is approved by ethics committee from all participating centers. All participants provide informed consent prior inclusion to the study. Once completed, results will be published in peer-reviewed journals.Trial registration numberClinicalTrials.gov (NCT03674424).
Highlights
Cisplatin-based neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for patients with non-metastatic muscle invasive bladder cancer (MIBC)
NAC has shown to provide a significant overall survival (OS) benefit when compared to surgery alone; a meta-analysis that included 11 trials and 3005 patients has proved that cisplatin-based NAC yields an absolute 5% benefit in terms of 5-year OS [3]
Nearly half of the patients diagnosed with nonmetastatic MIBC are unfit for cisplatin-based therapy, mostly due to pre-existing comorbidities or low performance status, and currently no alternative options of neoadjuvant treatment exist for these patients [4,5,6]
Summary
Cisplatin-based neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for patients with non-metastatic muscle invasive bladder cancer (MIBC). No predictive biomarkers for pathological complete response (pCR) are currently validated in clinical practice. Guidelines recommend cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy with bilateral pelvic lymph node dissection as the standard treatment for patients with nonmetastatic MIBC [1, 2]. Despite the survival benefit obtained by NAC, common clinical practice is confronted with unmet needs that must be addressed. Nearly half of the patients diagnosed with nonmetastatic MIBC are unfit for cisplatin-based therapy, mostly due to pre-existing comorbidities or low performance status, and currently no alternative options of neoadjuvant treatment exist for these patients [4,5,6]. No validated predictive biomarkers exist to identify which patients benefit from NAC and allow treatment individualization
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