| General information |
| Database: | DB00740 |
| Objective: | The results of the Iressa PanAsia Study (IPASS), which compared gefitinib and carboplatin/paclitaxel in previously untreated neversmokers and light exsmokers with advanced pulmonary adenocarcinoma were published previously. This report presents overall survival (OS) and efficacy according to epidermal growth factor receptor (EGFR) biomarker status |
| Authors: | Fukuoka M, et al |
| Title: | Biomarker analyses and final overall survival results from a phase III, randomized, openlabel, firstline study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non small cell lung cancer in Asia (IPASS). |
| Journal: | J Clin Oncol. |
| Year: | 2011 |
| PMID: | 21670455 |
| Trial Design |
| Clinical Trial Id: | NCT00322452 |
| Agent: | gefitinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | non small cell lung cancer |
| Cancer Subtype: | advanced non small cell lung cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | Biomarker analyses and final overall survival results from a phase III, randomized, openlabel, firstline study |
| Key Patients Feature: | patients of IPASS study |
| Biomarker: | EGFR mutation (amplification mutation refractory system; 437 patients evaluable), EGFR gene copy number (fluorescent in situ hybridization; 406 patients evaluable), and EGFR protein expression (immunohistochemistry; 365 patients evaluable). |
| Biomark Analysis: | EGFR mutations are the strongest predictive biomarker for PFS and tumor response to firstline gefitinib versus carboplatin/paclitaxel. The predictive value of EGFR gene copy number was driven by coexisting EGFR mutation (post hoc analysis). Treatment related differences observed for PFS in the EGFR mutation positive subgroup were not apparent for OS. |
| Control Group Info: | gefitinib versus carboplatin/paclitaxel |
| Treatment Info: | NA |
| Primary End Point: | Biomarker analyses and final overall survival results |
| Secondary End Point: | NA |
| Patients Number: | 1217 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 58.9% v 44.8% for gefitinib vesus carboplatin/paclitaxel, respectively |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | PFS was significantly longer with gefitinib versus carboplatin/paclitaxel (HR, 0.66; 95% CI, 0.50 to 0.88; P = .005). |
| Median OS A vs. C: | OS (954 deaths) was similar for gefitinib and carboplatin/paclitaxel with no significant difference between treatments overall (hazard ratio, 0.90; 95% CI, 0.79 to 1.02; P = .109) or in EGFR mutation-positive (HR, 1.00; 95% CI, 0.76 to 1.33; P = .990) or EGFR mutation-negative (HR, 1.18; 95% CI, 0.86 to 1.63; P = .309; treatment by EGFR mutation interaction P = .480) subgroups. |
| Adverse Event(agent arm): | NA |
| Conclusions: | EGFR mutations are the strongest predictive biomarker for PFS and tumor response to firstline gefitinib versus carboplatin paclitaxel. The predictive value of EGFR gene copy number was driven by coexisting EGFR mutation (post hoc analysis). Treatment related differences observed for PFS in the EGFR mutation positive subgroup were not apparent for OS. OS results were likely confounded by the high proportion of patients crossing over to the alternative treatment. |