Re: The Challenges of bacillus of Calmette-Guerin (BCG) Therapy for High Risk Non Muscle Invasive Bladder Cancer Treatment in Older Patients

2019 ◽  
Vol 201 (5) ◽  
pp. 836-836
Author(s):  
Tomas L. Griebling
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Cancer Treatment ◽  
Older Patients ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bcg Therapy ◽  
Muscle Invasive

The challenges of Bacillus of Calmette-Guerin (BCG) therapy for high risk non muscle invasive bladder cancer treatment in older patients

2018 ◽  
Vol 9 (5) ◽  
pp. 507-512 ◽  
Author(s):  
Marco Racioppi ◽  
Luca Di Gianfrancesco ◽  
Mauro Ragonese ◽  
Giuseppe Palermo ◽  
Emilio Sacco ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Cancer Treatment ◽  
Older Patients ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bcg Therapy ◽  
Muscle Invasive

S1605: Phase II trial of atezolizumab in BCG-unresponsive non-muscle invasive bladder cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. TPS4591-TPS4591 ◽  
Author(s):  
Parminder Singh ◽  
Tangen Catherine ◽  
Seth P. Lerner ◽  
David McConkey ◽  
Melissa Plets ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Invasive Bladder Cancer ◽  
Type I ◽  
Muscle Invasive Bladder Cancer ◽  
Primary Endpoints ◽  
Bcg Therapy ◽  
Muscle Invasive

TPS4591 Background: Radical cystectomy is the standard of care for patients with BCG-unresponsive high risk non-muscle invasive bladder cancer (NMIBC). Based on the reported efficacy of atezolizumab in metastatic urothelial carcinoma and the known expression of PD-L1 expression in NMIBC after BCG therapy, this trial will evaluate the activity of atezolizumab in BCG-unresponsive high risk NMIBC. Methods: This is a single arm phase II trial testing systemic atezolizumab (1200 mg IV) every 3 weeks for one year in 135 patients with BCG-unresponsive high risk NMIBC. The study will enroll 70 patients with CIS (with or without concomitant Ta/T1) and 65 with Ta/T1 only. Patients with CIS at baseline will undergo mandatory repeat biopsy at 6 months, and all other patients only for suspected recurrence. Patients with persistent CIS, high grade Ta/T1 recurrence or progression to muscle invasive or metastatic disease will be taken off treatment. The co-primary endpoints are: (1) complete response (CR) at 6 months in the CIS subgroup, and (2) event-free survival (EFS) at 18 months in the overall population. A hierarchical approach will be used to test the two co-primary endpoints. Secondary endpoints include duration of CR as well as progression-free, cystectomy-free, bladder cancer-specific and overall survival in all patients. Response will be correlated to expression of PD-L1 and CD8 by IHC, and to molecular subtypes and immune signatures by RNA-sequencing. Results: If ≥28 (40%) CIS patients respond, the agent will be considered promising. This design has a significance level of 4.6%, and a power of 96%. If the lower bound of the 90% confidence interval of the 18-month EFS excludes 20%, the investigators will conclude the regimen significantly improves EFS relative to historical data (type I error rate 0.05 and statistical power 0.93). Conclusion:Successful completion of this trial could lead to a new treatment paradigm for patients with BCG-unresponsive high risk NMIBC. Funding: NIH/NCI grants: CA180888, CA180819, CA180820, CA180821, and CA180863. Clinical trial information: NCT02844816.

scholarly journals Efficacy of HIVEC in patients with high-risk non-muscle invasive bladder cancer who are contraindicated to BCG and in patients who fail BCG therapy

2021 ◽  
Vol 38 (1) ◽  
pp. 1633-1638
Author(s):  
Laure Doisy ◽  
Arnaud Cimier ◽  
Aurélien Adypagavane ◽  
Jochen Walz ◽  
Thibault Marquette ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bcg Therapy ◽  
Muscle Invasive

scholarly journals Clinicopathological Criteria Predictive of Recurrence Following Bacillus Calmette-Guérin in Non–Muscle-Invasive Bladder Cancer (Preprint)

2020 ◽  
Author(s):  
Joseph Plasek ◽  
John Weissert ◽  
Tracy Downs ◽  
Kyle Richards ◽  
Kourosh Ravvaz
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Univariate Analysis ◽  
Neutrophil To Lymphocyte Ratio ◽  
Invasive Bladder Cancer ◽  
Bacillus Calmette Guerin ◽  
Muscle Invasive Bladder Cancer ◽  
Lymphocyte Ratio ◽  
Bcg Therapy ◽  
Muscle Invasive

BACKGROUND Bacillus Calmette-Guérin (BCG) is currently the most clinically effective intravesical treatment for non–muscle-invasive bladder cancer (NMIBC), particularly for patients with high-risk NMIBC such as those with carcinoma in-situ (CIS). BCG treatments could be optimized to improve patient safety and conserve supply by predicting BCG efficacy with tumor characteristics or clinicopathological criteria. OBJECTIVE To assess the ability of specific clinicopathological criteria to predict tumor recurrence in patients with NMIBC who received BCG along various treatment timelines. METHODS A total of 1331 patients (Stage Ta, T1, or CIS) who underwent transurethral resection of a bladder tumor (TUR) between 2006 and 2017 were included. Univariate analysis including laboratory tests (e.g. complete blood panels, creatinine levels, Hemoglobin A1c levels) within 180 days post-BCG therapy initiation, medications, and clinical and demographic variables to assess their ability to predict NMIBC recurrence was completed. This was followed by multivariate regression that included the elements of Club Urológico Español de Tratamiento Oncológico (CUETO) and variables that were significant predictors of recurrence in univariate analysis. RESULTS BCG was administered to 183 intermediate- or high-risk patients, and 76 (41.5%) experienced disease recurrence. Abnormal neutrophil-to-lymphocyte ratio measured within 180 days post-induction BCG was a significant predictor (p<0.05) of future cancer recurrence and was a stronger predictor than CUETO or the individual variables included in CUETO via multivariate analysis. CONCLUSIONS Abnormal neutrophil-to-lymphocyte ratio within 180 days following BCG is predictive of recurrence and could be a suggestive for additional or alternative interventions. CLINICALTRIAL N/A

Phase II trial of atezolizumab in BCG-unresponsive non-muscle invasive bladder cancer: SWOG S1605 (NCT #02844816).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5022-5022 ◽  
Author(s):  
Peter C. Black ◽  
Catherine Tangen ◽  
Parminder Singh ◽  
David James McConkey ◽  
Scott Lucia ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Phase Ii ◽  
Complete Response ◽  
Median Number ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Bladder Preservation ◽  
Bcg Therapy ◽  
Muscle Invasive

5022 Background: Radical cystectomy (RC) is the standard of care for patients with BCG-unresponsive high risk non-muscle invasive bladder cancer (NMIBC), but many patients are unfit for surgery or elect bladder preservation. Based on the reported efficacy of atezolizumab in metastatic urothelial carcinoma and the known expression of PD-L1 in NMIBC after BCG therapy, this trial was designed to evaluate the activity of atezolizumab in BCG-unresponsive high risk NMIBC. Methods: This single arm phase II registration trial testing systemic atezolizumab (1200 mg IV) every 3 weeks for one year aimed to enroll 135 (70 CIS and 65 non-CIS) eligible patients with histologically proven BCG-unresponsive high risk NMIBC who were unfit for or declined RC. Here we report on the subset with CIS (with or without concomitant Ta/T1) among patients who received at least one protocol treatment. The primary endpoint was pathological complete response (CR) rate at 6 months as defined by mandatory biopsy with a null hypothesis of 30% and alternative of 50% with a 1-sided alpha = 0.05 and 96% power. The 3 month CR rate, defined by cytology, cystoscopy and for-cause biopsy, is reported here as a secondary endpoint, in addition to safety. Results: Seventy-five eligible CIS patients were enrolled. Two received no treatment and are not evaluable. Of 73, median patient age was 73.4 years and median number of prior BCG doses was 12. Concomitant Ta/T1 tumor was found in 30 (41.1%) patients, including T1 disease in 16 (21.9%). A CR was observed in 30 (41.1%; 95% CI 29.7%, 53.2%) patients at 3 months and 19 (26.0%; 95% CI 16.5%, 37.6%) at 6 months. Any possibly or probably treatment-related adverse event (AE) was observed in 61 (83.6%) patients. The most frequent AEs were fatigue 36 (49.3%), pruritis 8 (11.0%), hypothyroidism 8 (11.0%), and nausea 8 (11.0%). Grade 3-5 AEs occurred in 9 (12.3%) patients and there was one treatment-related death (myasthenia gravis with respiratory failure and sepsis). Conclusion: The observed response to atezolizumab at 3 and 6 months in patients with BCG-unresponsive CIS was similar to that reported in recent similar trials and meets the benchmark for initial CR defined by the FDA guidance. This trial provided no new safety concerns. The duration of response will determine if this is a suitable treatment option for patients with BCG-unresponsive high risk CIS. Clinical trial information: 02844816 .

scholarly journals Protocol for phase I study of pembrolizumab in combination with Bacillus Calmette-Guérin for patients with high-risk non-muscle invasive bladder cancer

BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e028287 ◽  
Author(s):  
Marcus L Jamil ◽  
Mustafa Deebajah ◽  
Akshay Sood ◽  
Kathy Robinson ◽  
Krishna Rao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Phase I ◽  
Radical Cystectomy ◽  
Endoscopic Resection ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Safety And Efficacy ◽  
Bcg Therapy ◽  
Muscle Invasive

IntroductionThe initial treatment for high-risk non-muscle invasive bladder cancer (NMIBC) is endoscopic resection of the tumour followed by BCG therapy. In those who develop recurrence, the standard treatment is radical cystectomy. Despite the advancement in surgical technique and postoperative care, the degree of morbidity associated with radical cystectomy remains high, therefore less invasive treatment modalities are desirable. Therapies targeting the programmed death (PD) pathway have shown promise in urothelial carcinoma. We undertook the current study to determine the safety and efficacy of administering pembrolizumab (a monoclonal antibody targeting the interaction between PD-1 and its ligand) in combination with BCG in high-risk NMIBC.MethodsThis is a single-centre phase I safety and efficacy study of pembrolizumab used in combination with intravesicular BCG treatment for subjects with pathologically documented high-risk NMIBC despite having received two courses of induction therapy or BCG treatment followed by maintenance BCG. Fifteen subjects will be enrolled, patients will receive treatment with 200 mg of pembrolizumab every 21 days, starting 2 weeks from the initial endoscopic resection and continuing for 6 weeks after the final dose of BCG. The primary objective is to determine the safety of administering pembrolizumab at a fixed dose of 200 mg every 3 weeks in conjunction with intravesicular BCG treatment in patients with high-risk NMIBC who have failed previous treatment. Secondary objectives are to determine the 19 weeks and the 3, 12 and 24 months post-treatment completion complete response rate with combined pembrolizumab and intravesicular BCG therapy in the aforementioned patients.Ethics and disseminationThe study has been approved by the Institutional Review Board of the Henry Ford Hospital. The results of this study will be published in a peer-reviewed journal and presented at a scientific conference.Trial registration numberNCT02324582.

Sign in / Sign up

Export Citation Format

Share Document