Treatment of high-grade non-muscle invasive bladder carcinoma by standard number and dose of BCG instillations versus reduced number and standard dose of BCG instillations: Results of the phase III clinical trial (NIMBUS).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 436-436 ◽  
Author(s):  
Marc-Oliver Grimm ◽  
Toine van der Heijden ◽  
Marc Colombel ◽  
Luis Martinez Pineiro ◽  
Tim Muilwijk ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Prognostic Factors ◽  
Standard Dose ◽  
Intravesical Instillation ◽  
Optimal Number ◽  
Phase Iii ◽  
High Grade ◽  
First Recurrence ◽  
Muscle Invasive ◽  
Induction Cycle

436 Background: Intravesical instillation of BCG is an accepted strategy to prevent recurrence of non muscle invasive bladder cancer (NMIBC). However, the optimal number of instillations is unknown. NIMBUS assessed whether a reduced number/standard dose BCG instillations is not inferior to standard number and dose BCG in patients with high-grade (HG) NMIBC. The primary endpoint was time to first recurrence. Methods: The aim was to enroll 824 BCG naïve patients with HG Ta-T1 NMIBC +/- CIS. NIMBUS was an international randomized not blinded trial to establish therapeutic equivalence defined as the lower part of the Confidence Interval (CI) (using one-sided 2.5% level of significance) being higher than a HR (hazard experimental/hazard standard) of 0.75 for recurrence. The treatment arms were: Standard: Induction cycle BCG weekly wks 1-6; maintenance cycles at months 3,6,12 (wks 1,2,3) and Reduced: Induction cycle at wks 1,2,6; maintenance cycles at months 3,6,12 (wks 1,3). Safety was evaluated at yearly intervals by the IDMC and in case inferiority was shown, defined as the upper part of the CI (one-sided 2.5% level) lower than a HR of 0.75, an advice to stop the trial would be given. Results: Available data at July 1, 2019 were analyzed for the IDMC meeting. A total of 345 patients were recruited from Germany (149), the Netherlands (109), France (64), Belgium (22) and Spain (1). Prognostic factors at initial resection were Ta/T1: 46/54%; primary/recurrent disease: 92/8%; single/multiple lesions: 57/43% and concomitant CIS/no CIS: 27/73%. The intention to treat analysis showed a clear difference in time to and number of recurrences between treatment arms: 27% in the reduced arm versus 12% in the standard arm. Known prognostic factors were evenly distributed between arms. Additional safety analyses were performed showing a HR of 0.40 [95% CI: 0.24-0.67]. Conclusions: Safety analysis showed that the reduced frequency schedule of BCG was inferior to the standard frequency schedule for time to first recurrence according to the previously defined stop criterion. Recruitment of patients was stopped immediately. Clinical trial information: NTR4011.

Explored prognostic factors for survival in patients with advanced GIST treated with standard dose imatinib (IM): Results from the BFR14 phase III trial of the French Sarcoma Group.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10092-10092 ◽  
Author(s):  
David Pérol ◽  
Isabelle Ray-Coquard ◽  
Binh Bui Nguyen ◽  
Antoine Adenis ◽  
Maria Rios ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Tumor Cells ◽  
Cox Model ◽  
Standard Dose ◽  
Biological Significance ◽  
Phase Iii ◽  
Entire Cohort ◽  
Cd34 Expression ◽  
Advanced Gist

10092 Background: Factors predicting progression free survival (PFS) and overall survival (OS) of patients (pts) with advanced GIST treated with 400 mg daily dose IM included in the BFR14 study with a median follow up of 54 months (CI95%:47-61) was investigated evaluating added prognostic factors. Methods: 434 pts were included in this prospective multicenter trial from June 2002 to July 2009. After 1, 3 and 5 yrs of IM 400mg/day, pts free from progression were randomly offered to continue or interrupt (I arm) IM. Prognostic factors for overall survival were investigated in the entire cohort (randomized and not randomized pts) included in the BFR14. Survival was defined from the date of inclusion to the date of death for OS or to the first occurrence of disease progression under imatinib or death for PFS. A multivariate cox model including statistical significant baseline characteristics tested in univariate were included in a backward procedure d to identify independent prognostic factors for PFS then OS. Results: As of January 2012, there were 285 progressions (65%) and 161 deaths (37%). The median PFS of the entire cohort was 29 months (CI95%: 24-33) and the 4 and 5-yrs PFS were 31% and 24% respectively. A low tumour volume at inclusion, PS (0), sex (female), CD34 positivity on tumor cells were the four independent prognostic factors of a higher PFS. The 5-yrs OS was 54% (CI95%: 48-60). A higher OS was independently predicted by gender (female), PS (0), platelets count (<400 giga/L) and CD34 expression on GIST cells. Median PFS and OS were slightly superior in this more recent series as compared to B2222 consistently with the improved outcome of patients with low tumor volume. Conclusions: OS and PFS are predicted by gender, PS and CD34 expression in this large series of pts treated with standard dose IM. The biological significance of CD34 expression on tumor cells has to be explored in GIST.

scholarly journals TMPRSS2:ERG Gene Fusion Predicts Subsequent Detection of Prostate Cancer in Patients With High-Grade Prostatic Intraepithelial Neoplasia

2014 ◽  
Vol 32 (3) ◽  
pp. 206-211 ◽  
Author(s):  
Kyung Park ◽  
James T. Dalton ◽  
Ramesh Narayanan ◽  
Christopher E. Barbieri ◽  
Michael L. Hancock ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Gene Fusion ◽  
Intraepithelial Neoplasia ◽  
Prostatic Intraepithelial Neoplasia ◽  
Phase Iii ◽  
High Grade ◽  
Exact Test ◽  
Improve Risk Stratification

Purpose High-grade prostatic intraepithelial neoplasia (HGPIN) is considered a precursor lesion of prostate cancer (PCa). The predictive value of ERG gene fusion in HGPIN for PCa was interrogated as a post hoc analysis in the context of a randomized clinical trial. Patients and Methods The GTx Protocol G300104 randomly assigned 1,590 men with biopsy-diagnosed HGPIN to receive toremifene or placebo for 3 years or until a diagnosis of PCa was made on prostate biopsy. As part of this phase III clinical trial, a central pathologist evaluated biopsies of patients with isolated HGPIN at baseline and 12, 24, and 36 months of follow-up. ERG immunohistochemistry was performed on biopsies from 461 patients and evaluated for protein overexpression. Results ERG expression was detected in 11.1% of patients (51 of 461 patients) with isolated HGPIN. In the first year and during the 3-year clinical trial, 14.7% and 36.9% of 461 patients were diagnosed with PCa, respectively. Patients with ERG expression were more likely to develop PCa, with 27 (53%) of 51 ERG-positive and 143 (35%) of 410 ERG-negative patients experiencing progression to PCa (P = .014, Fisher's exact test). ERG expression was not associated with age, baseline PSA, Gleason score, or tumor volume. Conclusion This study underscores the necessity of more stringent follow-up for men with HGPIN that is also positive for ERG overexpression. Clinicians should consider molecular characterization of HGPIN as a means to improve risk stratification.

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