A Randomized, Phase II, Biomarker-Selected Study Comparing Erlotinib to Erlotinib Intercalated With Chemotherapy in First-Line Therapy for Advanced Non–Small-Cell Lung Cancer

• Published in: Journal of clinical oncology Vol. 29; no. 26; pp. 3567 - 3573
• Main Authors: HIRSCH, Fred R, KABBINAVAR, Fairooz, RUSK, Jason, FRANKLIN, Wilbur A, VARELLA-GARCIA, Marileila, BUNN, Paul A, ROSS CAMIDGE, D, EISEN, Tim, MARTINS, Renato, SCHNELL, Fredrick M, DZIADZIUSZKO, Rafal, RICHARDSON, Katherine, RICHARDSON, Frank, WACKER, Bret, STERNBERG, David W
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10.09.2011
• Subjects: Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Biomarkers, Pharmacological; Cadherins - metabolism; Carboplatin - administration & dosage; Carboplatin - adverse effects; Carcinoma, Non-Small-Cell Lung - blood; Carcinoma, Non-Small-Cell Lung - drug therapy; Chemotherapy; Drug Administration Schedule; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - genetics; ErbB Receptors - metabolism; Erlotinib Hydrochloride; Humans; Lung Neoplasms - blood; Lung Neoplasms - drug therapy; Medical sciences; Original Reports; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Pharmacology. Drug treatments; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins p21(ras); Quinazolines - administration & dosage; Quinazolines - adverse effects; Quinazolines - therapeutic use; ras Proteins - metabolism; Survival Analysis; Tumors; Vimentin - metabolism; Antineoplastic agent; Quinazoline derivatives; Lung cancer; non-small cell lung carcinoma; Epidermal growth factor receptor; Randomization; Cancerology; Taxane derivatives; Phase II trial; Paclitaxel; Bronchus disease; Advanced stage; Antimitotic; Protein-tyrosine kinase; Platinum II Complexes; Human; Lung disease; Drug combination; Enzyme; Tyrosine kinase inhibitor; Respiratory disease; Transferases; Enzyme inhibitor; Malignant tumor; First line treatment; Chemotherapy; Treatment; Erlotinib; Carboplatin; Comparative study; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2010.34.4929

Erlotinib prolongs survival in patients with advanced non-small-cell lung cancer (NSCLC). We report the results of a randomized, phase II study of erlotinib alone or intercalated with chemotherapy (CT + erlotinib) in chemotherapy-naïve patients with advanced NSCLC who were positive for epidermal growth factor receptor (EGFR) protein expression and/or with high EGFR gene copy number. A total of 143 patients were randomly assigned to either erlotinib 150 mg daily orally until disease progression (PD) occurred or to chemotherapy with paclitaxel 200 mg/m(2) intravenously (IV) and carboplatin dosed by creatinine clearance (AUC 6) IV on day 1 intercalated with erlotinib 150 mg orally on days 2 through 15 every 3 weeks for four cycles followed by erlotinib 150 mg orally until PD occurred (CT + erlotinib). The primary end point was 6-month progression-free survival (PFS); secondary end points included response rate, PFS, and survival. EGFR, KRAS mutation, EGFR fluorescent in situ hybridization and immunohistochemistry, and E-cadherin and vimentin protein levels were also assessed. Six-month PFS rates were 26% and 31% for the two arms (CT + erlotinib and erlotinib alone, respectively). Both were less than the historical control of 45% (P = .001 and P = .011, respectively). Median PFS times were 4.57 and 2.69 months, respectively. Patients with tumors harboring EGFR activating mutations fared better on erlotinib alone (median PFS, 18.2 months v 4.9 months for CT + erlotinib). The feasibility of a multicenter biomarker-driven study was demonstrated, but neither treatment arms exceeded historical controls. This study does not support combined chemotherapy and erlotinib in first-line treatment of EGFR-selected advanced NSCLC, and the patients with tumors harboring EGFR mutations had a better outcome on erlotinib alone.