Entry Detail
| General information | |
| Database: | DB00928 |
| Objective: | This trial evaluated the efficacy and safety of sorafenib plus gemcitabine/cisplatin in chemotherapynaive patients with unresectable stage IIIB to IV nonsquamous non small cell lung cancer (non small cell lung cancer). |
| Authors: | PazAres LG, et al |
| Title: | Phase III, randomized, doubleblind, placebocontrolled trial of gemcitabine/cisplatin alone or with sorafenib for the firstline treatment of advanced, nonsquamous non small cell lung cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2012 |
| PMID: | 22851564 |
| Trial Design | |
| Clinical Trial Id: | NCT00449033 |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced nonsquamous non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | gemcitabine/cisplatin with sorafenib |
| Study Type: | Phase III, randomized, doubleblind, placebocontrolled trial |
| Key Patients Feature: | chemotherapynaive patients with unresectable stage IIIB to IV nonsquamous non small cell lung cancer (non small cell lung cancer |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | gemcitabine/cisplatin alone versus gemcitabine/cisplatin with sorafenib |
| Treatment Info: | patients were randomly assigned to daily sorafenib (400 mg twice a day) or matching placebo plus gemcitabine (1, 250 mg/m(2) per day on days 1 and 8) and cisplatin (75 mg/m(2) on day 1) for up to six 21day cycles |
| Primary End Point: | overall survival (OS) |
| Secondary End Point: | progression free survival (PFS) and timetoprogression (TTP). |
| Patients Number: | 904 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | in the sorafenib plus gemcitabine/cisplatin and placebo plus gemcitabine/cisplatin groups were 28% and 26%, respectively |
| Disease Control Rate: | in the sorafenib plus gemcitabine/cisplatin and placebo plus gemcitabine/cisplatin groups: DCRs (CR + PR + SD) were 62% and 63%, respectively (P = .39). |
| Median Time to Progression: | sorafenib improved median TTP (6.1 v 5.5 months; HR, 0.73; P < .001). |
| Median PFS A vs. C: | sorafenib improved median PFS (6.0 v 5.5 months; HR, 0.83; P = .008) |
| Median OS A vs. C: | Median OS was similar in the sorafenib and placebo groups (12.4 v 12.5 months; hazard ratio [HR], 0.98; P = .401) |
| Adverse Event(agent arm): | Grade 3 to 4 drugrelated adverse events more than twofold higher in the sorafenib group included handfoot skin reaction (8.6% v 0.3%), fatigue (7.3% v 3.6%), rash (5.7% v 0.5%), and hypertension (4.2% v 1.8%). No unexpected toxicities were observed. |
| Conclusions: | This study did not meet its primary end point of improved OS when sorafenib was added to firstline gemcitabinecisplatin in patients with advanced nonsquamous non small cell lung cancer. Identification of predictive biomarkers is warranted in future trials of sorafenib |