| General information |
| Database: | DB00552 |
| Objective: | Epidermal growth factor receptor overexpression is associated with poor outcomes in urothelial carcinoma (UC). Cetuximab (CTX) exhibited an antitumor effect in in vivo UC models. The efficacy of gemcitabine/cisplatin (GC) with or without CTX in patients with advanced UC was evaluated. |
| Authors: | Hussain M, et al |
| Title: | A randomizedphase 2 trial of gemcitabine/cisplatin with or without cetuximab in patients with advanced urothelial carcinoma. |
| Journal: | cancer |
| Year: | 2014 |
| PMID: | 24802654 |
| Trial Design |
| Clinical Trial Id: | NCT00645593 |
| Agent: | Cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | Urothelial Carcinoma |
| Cancer Subtype: | advanced urothelial carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | gemcitabine/cisplatin with or without cetuximab |
| Study Type: | Randomizedphase II Trial |
| Key Patients Feature: | Eligible patients had a pathological diagnosis of UC (pureor mixed histology) from primary, metastatic, locallyrecurrent, or locally advanced/unresectable (T4bN0 orTanyN23) and measurable bladder or nonbladder disease on imaging; an Eastern Cooperative OncologyGroup performance status 2; a life expectancy 12weeks; and adequate organ function (absolute neutrophilcount 1500 lL, platelet count 1500 lL, serum creatinine level 1.5 mg/dL or creatinine clearance 50 mL/min, and total bilirubin level 1.5 mg/dL). Prior neoadjuvant or adjuvant chemotherapy was allowed if 6 monthsor more had passed since a non-cisplatinbased regimenor 1 year or more had passed since a cisplatinbased regimen. Patients with an asymptomatic pulmonary embolus or deep vein thrombosis (DVT) were eligible if they wereon anticoagulation and at the physician¡¯s discretion |
| Biomarker: | soluble Ecadherin level |
| Biomark Analysis: | An increased soluble Ecadherin level after cycle 2 correlated with a higher risk of death. |
| Control Group Info: | gemcitabine/cisplatin with or without cetuximab |
| Treatment Info: | patients were randomized 1:2 to cisplatin (70 mg/m(2) ) on day 1 plus gemcitabine (1000 mg/m(2) ) on days 1, 8, and 15 (arm A) or GC plus CTX (500 mg/m(2) ) on days 1 and 15 (arm B). |
| Primary End Point: | overall response rate. |
| Secondary End Point: | the response duration, safety, progression free survival, overall survival, determination of whether or not CTX sensitized nonresponders to GC, and exploratory biomarker analysis. |
| Patients Number: | 88 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The overall response rates were 57.1% for arm A (95% CI = 37%76%) and 61.4% for arm B (95% CI = 48%74%). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 8.5 months for arm A (95% CI = 5.7-10.4 months) and 7.6 months for arm B (95% CI = 6.1-8.7 months). |
| Median OS A vs. C: | 17.4 months for arm A (95% CI = 12.8 months to unreached) and 14.3 months for arm B (95% CI = 11.6-22.2 months). |
| Adverse Event(agent arm): | The most common grade 3/grade 4 adverse events in both arms were myelosuppression and nausea. Thromboembolism, acneiform rash, fatigue, pain, hypersensitivity reactions, elevated transaminases, hyponatremia, and hypomagnesemia were more common in arm B; 3 grade 5 adverse events occurred in arm B. The presence of primary disease significantly correlated with thromboembolism. An increased soluble Ecadherin level after cycle 2 correlated with a higher risk of death. |
| Conclusions: | GC plus CTX was feasible but was associated with more adverse events and no improvements in outcomes. |