A randomized phase 2 trial of erlotinib versus pemetrexed as second‐line therapy in the treatment of patients with advanced EGFR wild‐type and EGFR FISH‐positive lung adenocarcinoma

• Published in: Cancer 2014-05, Vol.120 (9), p.1379-1386
• Main Authors: Li, Ning, Ou, Wei, Yang, Hua, Liu, Qian‐Wen, Zhang, Song‐Liang, Wang, Bao‐Xiao, Wang, Si‐Yu
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - enzymology; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adenocarcinoma of Lung; Adult; Aged; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; Biological and medical sciences; epidermal growth factor receptor (EGFR) copy number; ErbB Receptors - biosynthesis; ErbB Receptors - genetics; erlotinib; Erlotinib Hydrochloride; Female; Gene Dosage; Glutamates - adverse effects; Glutamates - therapeutic use; Guanine - adverse effects; Guanine - analogs & derivatives; Guanine - therapeutic use; Humans; In Situ Hybridization, Fluorescence; Lung Neoplasms - drug therapy; Lung Neoplasms - enzymology; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Staging; non‐small cell lung cancer; Pemetrexed; Pneumology; Protein Kinase Inhibitors - adverse effects; Protein Kinase Inhibitors - therapeutic use; Quinazolines - adverse effects; Quinazolines - therapeutic use; second‐line therapy; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.28591

BACKGROUND The current study was undertaken to investigate the efficacy and safety of erlotinib versus pemetrexed as second‐line therapy for patients with advanced epidermal growth factor receptor (EGFR) wild‐type and EGFR fluorescence in situ hybridization (FISH)‐positive lung adenocarcinoma. METHODS In this open‐label, randomized, phase 2 study, patients with EGFR wild‐type and EGFR FISH‐positive adenocarcinoma who had developed disease progression after 1 prior platinum‐based chemotherapy were randomly assigned (1:1) to receive erlotinib or pemetrexed until the time of disease progression or death, unacceptable toxicity, or a request for discontinuation by the patient. The primary endpoint was progression‐free survival (PFS). RESULTS A total of 123 patients were enrolled (61 in the erlotinib arm and 62 in the pemetrexed arm). The median PFS was 4.1 months (95% confidence interval [95% CI], 1.6 months‐6.6 months) in the erlotinib group versus 3.9 months (95% CI, 2.7 months‐5.1 months) in the pemetrexed group. The difference in PFS between the 2 treatment groups was not significant (hazard ratio, 0.92; 95% CI, 0.62‐1.37 [P = .683]). The objective response rate appeared to be higher among patients receiving erlotinib compared with those receiving pemetrexed (19.7% vs 8.1%; P = .062). The 3 most commonly recorded adverse events were rash (54.1%), fatigue (19.7%), and diarrhea (16.4%) in the erlotinib group and fatigue (25.8%), nausea (24.2%), and anorexia (14.5%) in the pemetrexed group. CONCLUSIONS There were no significant differences noted with regard to efficacy between erlotinib and pemetrexed in the second‐line setting for patients with advanced EGFR wild‐type and EGFR FISH‐positive lung adenocarcinoma. Both regimens appear to be effective treatment options for these patients. Cancer 2014;120:1379–1386. © 2014 American Cancer Society. The results of the current randomized phase 2 trial demonstrate that there are no significant differences in efficacy between erlotinib and pemetrexed in the second‐line setting for patients with advanced epidermal growth factor receptor wild‐type and epidermal growth factor receptor fluorescence in situ hybridization‐positive lung adenocarcinoma, and both regimens are effective treatment options in the second‐line setting for these patients.