scholarly journals Cabazitaxel in Platinum Pre-treated Patients with Locally Advanced or Metastatic Transitional Cell Carcinoma Who Developed Disease Progression after Platinum based Chemotherapy: Results of the Phase II CAB-B1 Trial

2019 ◽  
Vol 4 (4) ◽  
Keyword(s):  
Transitional Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Controlled Trial ◽  
Locally Advanced ◽  
Transitional Cell ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Platinum Based Chemotherapy ◽  
Randomised Controlled

There is a paucity of chemotherapy options for patients with urothelial cancers who have relapsed following platinum based chemotherapy (CT). CAB-B1 was a single centre phase II randomised controlled trial of Cabazitaxel (CAB; 25mg/m2 q3 week for 6 cycles) versus best supportive care (BSC) in patients with histologically proven transitional cell carcinoma (TCC), locally advanced or metastatic, who had recurred after receiving platinum based treatment. Primary outcome was overall response rate (ORR) using RESIST. Secondary outcomes included Progression Free Survival (PFS) and Overall Survival (OS). Between January 2013 and October 2016, 20 patients were randomised (10 on each arm). BSC included paclitaxel CT for 9 patients and radiotherapy for 1 patient. 8 patients completed 6 cycles of CT (3 on CAB; 5 on BSC). 2 patients had an ORR on CAB and 1 patient on BSC. Median OS was 5.8 months (95% confidence interval (CI) 0.7-14.6) for CAB patients and 7.5 months (95% CI 1.0-10.8) for BSC patients. Median PFS was 4.8 months (95% CI 0.7-8.3) for CAB patients and 3.7 months (95% CI 1.0-7.0) for BSC patients. CAB-B1 successfully reached the efficacy target for 1st stage, showing that there could be a role for CAB in these patients.

Cabazitaxel in patients with locally advanced or metastatic transitional cell carcinoma who developed disease progression within 12 months of platinum based chemotherapy: Results of a phase II trial—CAB-B1.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4542-4542
Author(s):  
Anjali Zarkar ◽  
Andrea Marshall ◽  
Janet Dunn ◽  
Amanda Davies ◽  
Daniel Ford ◽  
...  
Keyword(s):  
Transitional Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Locally Advanced ◽  
Transitional Cell ◽  
Life Assessment ◽  
Stopping Rules ◽  
Single Centre ◽  
Platinum Based Chemotherapy ◽  
Alpha Level

4542 Background: There is a paucity of chemotherapy options for the treatment of patients who have relapsed following platinum based chemotherapy (CT). Cabazitaxel is a new taxane that showed in-vivo antiproliferative activity on resistant cell lines. Methods: CAB-B1 was a single centre phase II randomised controlled trial of Cabazitaxel (CAB; 25mg/m2 q3 week for 6 cycles) versus best supportive care (BSC) in patients (pts) with histologically proven transitional cell carcinoma (TCC), locally advanced or metastatic, who had received platinum based treatment and recurred within 12 months of the last cycle of CT. Primary outcome was overall response rate (ORR) using RESIST. Secondary outcomes were Progression Free Survival (PFS), Overall Survival (OS), Quality of Life assessment, safety and tolerability. A total of 96 pts required to detect differences in ORR from 5% to 30%; 80% power; 5% alpha level; 10% dropouts. Stopping rules, using Simon’s two stage optimal design to assess the individual effectiveness of CAB, required at least 1 ORR from 10 pts on CAB during 1st stage (i.e. total of 20 pts randomised) and 4 from 29 CAB pts in 2nd stage (assuming lower ORR limit of 0.05, target ORR of 0.20, 80% power, 5% alpha level). The trial was supported by grant from Sanofi. Results: Between January 2013 and October 2016, 20 pts were randomised (10 on each arm). 75% males; median age 68 years; 65% had recurred within 6 months of previous CT. BSC included paclitaxel CT for 9 pts and radiotherapy for 1 pt. 8 pts completed 6 cycles of CT (3 on CAB; 5 on BSC). 6 pts on each arm were evaluated for response after having 2/3 cycles; 2 pts had an ORR on CAB and 1 pt on BSC. 14 pts have died of disease (8 on CAB; 6 on BSC).Median OS was 5.6 months (95% confidence interval (CI) 0.7-15.2) for CAB pts and 8.2 months (95% CI 1.0-8.8) for BSC pts. Median PFS was 4.4 months (95% CI 0.7-9.4) for CAB pts and 4.1 months (95% CI 1.0-6.8) for BSC pts. Conclusions: It has been hard to recruit these poorly patients within a single centre, but CAB-B1 successfully reached the efficacy target for the 1st stage, showing that there could be a role for CAB in these pts. Clinical trial information: NCT01668459.

Results of the GETUG-AFU 19 trial: A randomized phase II study of dose dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) with or without anti-epidermal growth factor receptor (EGF-R) monoclonal antibody panitumumab (PANI) in advanced transitional cell carcinoma (ATCC).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 307-307 ◽  
Author(s):  
Stephane Culine ◽  
Aude Flechon ◽  
Gwenaelle Gravis ◽  
Guilhem Roubaud ◽  
Yohann Loriot ◽  
...  
Keyword(s):  
Transitional Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mrna Level ◽  
Locally Advanced ◽  
Transitional Cell ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Median Number ◽  
Upper Urinary Tract ◽  
Significant Difference

307 Background: Frequent overexpression and correlation with stage and survival has been reported with the EGF-R pathway in ATCC. Methods: 93 patients (pts) with locally advanced or metastatic bladder or upper urinary tract (UUT) transitional cell carcinoma were planned with a 1:2 randomisation ratio. Patients with K-Ras or H-Ras mutations were excluded. dd-MVAC included M 30 mg/m2d1, V 3 mg/m2d2, D 30 mg/m2d2 and cisplatin 70 mg/m2d2 (d1 = d14) with G-CSF support. PANI 6 mg/kg was given on d2. The number of pts was determined from the 9-month median progression-free survival (PFS) rate reported with dd-MVAC. Using a one stage Fleming design, the dd-MVAC+PANI combination will be considered to be active if at least 37 patients among 70 do not show tumor progression at 9 months (p0 = 0.50, p1 = 0.70, alpha = 0.08 and beta = 0.03). As basal-like subtype might be related to Anti-EGFR treatment response, the phenotype was determined using a Keratin 5/6 and GATA3 double immunostaining (8 basal like among 58 cases tested). Results: From September 2010 to November 2015, 96 patients (bladder 68, UUT 21, both 8) received dd-MVAC (33) or dd-MVAC+PANI (63). No significant difference was observed among baseline characteristics and prognostic factors. The median number of cycles was 6 (1-6) in both arms. At least one grade > 2 toxicity was observed in 79% and 76% of patients in the dd-MVAC and PANI arms, respectively. More dermatological adverse events were observed in the PANI arm. Objective responses were reported in 23 (70%) pts in the dd-MVAC arm and 30 pts (48%) in the PANI arm. With a median follow-up of 27 months, PFS was 6.8 months and 5.7 months in the dd-MVAC and PANI arms respectively; OS was 20.2 months and 12.5 months in the dd-MVAC and PANI arms, respectively. No association was observed between PFS and basal-like feature for patients treated by MVAC+PANI. Molecular subtyping is in progress to confirm this observation at mRNA level. Conclusions: When combined with dd-MVAC, PANI does not seem to improve efficacy in pts with ATCC. Clinical trial information: NCT02818725.

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