scholarly journals 776P Phase II trial of concurrent nivolumab in urothelial bladder cancer with radiation therapy in localized/locally advanced disease for chemotherapy ineligible patients [NUTRA trial]

2020 ◽  
Vol 31 ◽  
pp. S596
Author(s):  
U.N. Vaishampayan ◽  
L.K. Heilbrun ◽  
N. Vaishampayan ◽  
C. Li ◽  
D. Shi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radiation Therapy ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Advanced Disease ◽  
Locally Advanced ◽  
Urothelial Bladder Cancer ◽  
Locally Advanced Disease ◽  
Urothelial Bladder

scholarly journals Efficacy of neoadjuvant atezolizumab treatment in patients with advanced urothelial bladder cancer according to the BASQ classification: a study protocol for an open-label, two-cohort, phase II trial

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e035530
Author(s):  
Hyeong Dong Yuk ◽  
Chang Wook Jeong ◽  
Cheol Kwak ◽  
Hyeon Kim ◽  
Kyung Chul Moon ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Radical Cystectomy ◽  
Phase Ii ◽  
Study Protocol ◽  
Phase Ii Trial ◽  
Urothelial Bladder Cancer ◽  
Open Label ◽  
End Point ◽  
Urothelial Bladder

IntroductionAtezolizumab is a programmed death ligand-1 inhibitor for urothelial bladder cancer treatment. Atezolizumab has become the standard therapy for patients with urothelial bladder cancer who are not responding to cisplatin-based chemotherapy and is also used as a first-line treatment in cisplatin-ineligible patients. However, the efficacy of atezolizumab as a neoadjuvant chemotherapy for radical cystectomy has not yet been published and is still under study. This trial investigates the effectiveness of basal/squamous-like (BASQ) classification in the selection of an effective target group of patients with muscle-invasive bladder cancer (MIBC) for neoadjuvant atezolizumab treatment.Methods and analysisThis study is an open-label, two-cohort, phase II trial. It was designed to evaluate the efficacy of neoadjuvant atezolizumab treatment in patients with MIBC (T2–4N0M0) pathological responses after neoadjuvant chemotherapy and radical cystectomy. According to the molecular subtype characteristics of previous transurethral resection of the bladder specimens, patients are divided into two groups: luminal type (KRT5/6−KRT14−FOXA1+GATA3+) and basal type (KRT5/6+KRT14+FOXA1−GATA3−). Every 3 weeks, atezolizumab is administered at a dose of 1200 mg for three cycles prior to radical cystectomy in patients with MIBC. The primary end point is objective pathological responses in the intention-to-treat patients. The secondary end point is a 1-year progression-free survival difference according to the BASQ classification in patients who underwent neoadjuvant atezolizumab treatment.Ethics and disseminationThe study protocol was approved by the Institutional Review Board of Seoul National University Hospital, Seoul, Republic of Korea (H 1806-051-950). The trial is registered at ClinicalTrials.gov. The trial results will be published in peer-reviewed journals and at conferences.Trial registration numberNCT03577132.

Combination of AST to ALT and neutrophils to lymphocytes ratios as predictors of locally advanced disease in patients with bladder cancer subjected to radical cystectomy: Results from a single-institutional series

2021 ◽  
pp. 039156032110351
Author(s):  
Alessandro Uleri ◽  
Rodolfo Hurle ◽  
Roberto Contieri ◽  
Pietro Diana ◽  
Nicolòmaria Buffi ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Advanced Disease ◽  
Independent Predictor ◽  
Small Sample Size ◽  
Statistical Significance ◽  
Locally Advanced ◽  
Small Sample ◽  
Locally Advanced Disease ◽  
Increased Risk

Background: Bladder cancer (BC) staging is challenging. There is an important need for available and affordable predictors to assess, in combination with imaging, the presence of locally-advanced disease. Objective: To determine the role of the De Ritis ratio (DRR) and neutrophils to lymphocytes ratio (NLR) in the prediction of locally-advanced disease defined as the presence of extravescical extension (pT ⩾ 3) and/or lymph node metastases (LNM) in patients with BC treated with radical cystectomy (RC). Methods: We retrospectively analyzed clinical and pathological data of 139 consecutive patients who underwent RC at our institution. Logistic regression models (LRMs) were fitted to test the above-mentioned outcomes. Results: A total of 139 consecutive patients underwent RC at our institution. Eighty-six (61.9%) patients had a locally-advanced disease. NLR (2.53 and 3.07; p = 0.005) and DRR (1 and 1.17; p = 0.01) were significantly higher in patients with locally-advanced disease as compared to organ-confined disease. In multivariable LRMs, an increasing DRR was an independent predictor of locally-advanced disease (OR = 3.91; 95% CI: 1.282–11.916; p = 0.017). Similarly, an increasing NLR was independently related to presence of locally-advanced disease (OR = 1.28; 95% CI: 1.027–1.591; p = 0.028). In univariate LRMs, patients with DRR > 1.21 had a higher risk of locally advanced disease (OR = 2.83; 95% CI: 1.312–6.128; p = 0.008). Similarly, in patients with NLR > 3.47 there was an increased risk of locally advanced disease (OR = 3.02; 95% CI: 1.374–6.651; p = 0.006). In multivariable LRMs, a DRR > 1.21 was an independent predictor of locally advanced disease (OR = 2.66; 95% CI: 1.12–6.35; p = 0.027). Similarly, an NLR > 3.47 was independently related to presence of locally advanced disease (OR = 2.24; 95% CI: 0.95–5.25; p = 0.065). No other covariates such as gender, BMI, neoadjuvant chemotherapy or diabetes reached statistical significance. The AUC of the multivariate LRM to assess the risk of locally advanced disease was 0.707 (95% CI: 0.623–0.795). Limitations include the retrospective nature of the study and the relatively small sample size.

Consolidative radiotherapy for metastatic urothelial bladder cancer patients without progression and with no more than three residual metastatic lesions following first line systemic therapy: A prospective randomized comparative phase II trial (BLAD RAD01/GETUG-AFU V07).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS4588-TPS4588
Author(s):  
Jonathan Khalifa ◽  
Damien Pouessel ◽  
Mathieu Roumiguie ◽  
Paul Sargos ◽  
Genevieve Loos ◽  
...  
Keyword(s):  
Phase Ii ◽  
Systemic Therapy ◽  
Phase Ii Trial ◽  
Local Treatment ◽  
Standard Of Care ◽  
Urothelial Bladder Cancer ◽  
First Line ◽  
Metastatic Lesions ◽  
Urothelial Bladder ◽  
Consolidative Radiotherapy

TPS4588 Background: Consolidative local treatment of the primary tumor in the treatment of metastatic malignancies has shown promising results in several types of tumors, mostly relying on the seed-and-soil theory. Furthermore, the local treatment of the residual metastases following systemic treatment is a promising approach, in part due to the high incidence of progression at prior sites of disease in patients who had initially responded to chemotherapy. To date, no prospective data exists on such consolidative approach in metastatic urothelial bladder cancer (mUBC). The phase II trial BLAD-RAD01 GETUG-AFU V07 was designed to investigate the role of local consolidative radiotherapy in patients with limited mUBC and without progression following the initial phase of first-line systemic therapy. Methods: This is a phase II, multicenter, randomized open-label and comparative study. Patients with mUBC (excluding brain and liver metastases), without progression following standard first-line systemic therapy according to RECIST v1.1, and with no more than 3 residual metastatic lesions on 18FDG-PET scanner and/or contrast-enhanced CT-scanner are eligible for the study. After the completion of systemic treatment, an estimated 130 patients will be randomized in a 1:1 ratio between consolidative local treatment (pelvic radiotherapy +/- previous transurethal resection of bladder tumor, associated with stereotactic body radiotherapy (SBRT) to the residual metastases) plus standard of care (arm B) and standard of care only (arm A). Stratification is performed based upon: the center, the ECOG performance status, the administration of immunotherapy or not, the number of residual metastatic lesions and the imaging modality for assessment of the number of residual lesions. To date, standard of care for this population is maintenance treatment with avelumab. Radiotherapy regimens consist in conventionally fractionated (64Gy in 32 fractions) or hypofractionated (55Gy in 20 fractions) irradiation of the bladder, optional pelvic nodes irradiation, and 3 to 5 fractions of 6 to 18 Gy in SBRT for metastases, depending on the location. The main objective is to detect an increase in 20-month overall survival rate following chemotherapy from 50% (based upon the JAVELIN 100 trial) to 66%; this corresponds to a hazard ratio of 0.6. A total of 83 events are necessary for 85% power to detect this difference if it is true using a one-sided logrank test at the 10% of significance. Target difference, type I and II error rates are relaxed and compatibles with recommendations for comparative phase II trials. Key secondary endpoints are progression free survival, safety and quality of life. To date, one patient has been enrolled and eight centers are open for accrual. Clinical trial information: NCT04428554.

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