Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer

• Verfasst von: Douillard, Jean-Yves [VerfasserIn]
• Verfasst von: Shepherd, Frances A. [VerfasserIn]
• Verfasst von: Hirsh, Vera [VerfasserIn]
• Verfasst von: Mok, Tony [VerfasserIn]
• Verfasst von: Socinski, Mark A. [VerfasserIn]
• Verfasst von: Gervais, Radj [VerfasserIn]
• Verfasst von: Liao, Mei-Lin [VerfasserIn]
• Verfasst von: Bischoff, Helge [VerfasserIn]
• Verfasst von: Reck, Martin [VerfasserIn]
• Verfasst von: Sellers, Mark V. [VerfasserIn]
• Verfasst von: Watkins, Claire L. [VerfasserIn]
• Verfasst von: Speake, Georgina [VerfasserIn]
• Verfasst von: Armour, Alison A. [VerfasserIn]
• Verfasst von: Kim, Edward S. [VerfasserIn]
• Titel: Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer
• Titelzusatz: data from the randomized phase III INTEREST trial
• Verf.angabe: Jean-Yves Douillard, Frances A. Shepherd, Vera Hirsh, Tony Mok, Mark A. Socinski, Radj Gervais, Mei-Lin Liao, Helge Bischoff, Martin Reck, Mark V. Sellers, Claire L. Watkins, Georgina Speake, Alison A. Armour, and Edward S. Kim
• Jahr: 2010
• Umfang: 9 S.
• Fussnoten: Published online ahead of print at www.jco.org on December 28, 2009 ; Gesehen am 16.02.2023
• Titel Quelle: Enthalten in: Journal of clinical oncology
• Ort Quelle: Alexandria, Va. : American Society of Clinical Oncology, 1983
• Jahr Quelle: 2010
• Band/Heft Quelle: 28(2010), 5, Seite 744-752
• ISSN Quelle: 1527-7755
• DOI: doi:10.1200/JCO.2009.24.3030
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1836330316

Abstract

Purpose: In the phase III INTEREST trial, 1,466 pretreated patients with advanced non-small cell lung cancer (NSCLC) were randomly assigned to receive gefitinib or docetaxel. As a preplanned analysis, we prospectively analyzed available tumor biopsies to investigate the relationship between biomarkers and clinical outcomes. - Methods: Biomarkers included epidermal growth factor receptor (EGFR) copy number by fluorescent in situ hybridization (374 assessable samples), EGFR protein expression by immunohistochemistry (n = 380), and EGFR (n = 297) and KRAS (n = 275) mutations. - Results: For all biomarker subgroups analyzed, survival was similar for gefitinib and docetaxel, with no statistically significant differences between treatments and no significant treatment by biomarker status interaction tests. EGFR mutation-positive patients had longer progression-free survival (PFS; hazard ratio [HR], 0.16; 95% CI, 0.05 to 0.49; P = .001) and higher objective response rate (ORR; 42.1% v 21.1%; P = .04), and patients with high EGFR copy number had higher ORR (13.0% v 7.4%; P = .04) with gefitinib versus docetaxel. - Conclusion: These biomarkers do not appear to be predictive factors for differential survival between gefitinib and docetaxel in this setting of previously treated patients; however, subsequent treatments may have influenced the survival results. For secondary end points of PFS and ORR, some advantages for gefitinib over docetaxel were seen in EGFR mutation-positive and high EGFR copy number patients. There was no statistically significant difference between gefitinib and docetaxel in biomarker-negative patients. This suggests gefitinib can provide similar overall survival to docetaxel in patients across a broad range of clinical subgroups and that EGFR biomarkers such as mutation status may additionally identify which patients are likely to gain greatest PFS and ORR benefit from gefitinib.