| General information |
| Database: | DB00087 |
| Objective: | to evaluates the efficacy and safety of erlotinib plus sorafenib, in patients with previously untreated advanced non small cell lung cancer. |
| Authors: | Lind JS, et al |
| Title: | A multicenterphase II study of erlotinib and sorafenib in chemotherapynaive patients with advanced non small cell lung cancer. |
| Journal: | Clin Cancer Res. |
| Year: | 2010 |
| PMID: | 20395213 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | sorafenib, erlotinib
|
| Target: | a smallmolecule multitargeted kinase inhibitor that blocks the activation of CRAF, BRAF, cKIT, FLT3, RET, vascular endothelial growth factor receptor 2 (VEGFR2), VEGFR3 and plateletderived growth factor receptor ¦Â
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | erlotinib+sorafenib |
| Study Type: | A multicenter, phase II study |
| Key Patients Feature: | Chemotherapyna ve patients with stage IIIB/IV non small cell lung cancer |
| Biomarker: | EGFR and KRAS mutation status;cytochrome P450 polymorphisms |
| Biomark Analysis: | Patients with wildtype EGFR had a higher ORR (19%) than previously reported for singleagent erlotinib/sorafenib. Erlotinib levels were lowered. This was associated with CYP3A4 polymorphism and was possibly due to sorafenib. |
| Control Group Info: | single arm |
| Treatment Info: | pts received erlotinib (150 mg once a day) and sorafenib (400 mg twice a day) until disease progression or unacceptable toxicity. |
| Primary End Point: | the rate of nonprogression at 6 weeks. |
| Secondary End Point: | ORR, time to progression, OS, and adverse events. Exploratory end points included pretreatment EGFR and KRAS mutation status, pharmacokinetics, and cytochrome P450 polymorphisms |
| Patients Number: | 55 |
| Trial Results |
| DLT_MTD: | erlotinib (150 mg once a day) and sorafenib (400 mg twice a day) until disease progression or unacceptable toxicity |
| Objective Response Rate: | 28%, patients with wildtype EGFR had a higher ORR (19%) than previously reported for singleagent erlotinib/sorafenib |
| Disease Control Rate: | The nonprogression rate at 6 weeks was 74%: 12 (24%) partial response and 25 (50%) stable disease. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median time to progression was 5.0[(95% CI), 3.26.8]. |
| Median OS A vs. C: | Median overall survival was 10.9 months (95% CI, 3.818.1). |
| Adverse Event(agent arm): | Grade 3/4 adverse events included fatigue (16%), handfoot skin reaction (16%), rash (16%), diarrhea (14%), and hypophosphatemia (42%). There was one treatmentrelated fatal pulmonary hemorrhage. |
| Conclusions: | Despite a possible drug interaction, sorafenib plus erlotinib has promising clinical activity in patients with stage IIIBIV non small cell lung cancer and has an acceptable safety profile. Further evaluation of this combination as potential salvage therapy in EGFR mutation-negative patients and the possible drug interaction is warranted. |