SWOG S0709: Randomized Phase II Trial of Erlotinib versus Erlotinib Plus Carboplatin/Paclitaxel in Patients with Advanced Non–Small Cell Lung Cancer and Impaired Performance Status as Selected by a Serum Proteomics Assay

• Published in: Journal of thoracic oncology 2016-03, Vol.11 (3), p.420-425
• Main Authors: Lara, Primo N., Moon, James, Hesketh, Paul J., Redman, Mary W., Williamson, Stephen K., Akerley, Wallace L., Hirsch, Fred R., Mack, Philip C., Gandara, David R.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carboplatin - administration & dosage; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cohort Studies; Erlotinib Hydrochloride - administration & dosage; Erlotinib Hydrochloride - therapeutic use; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Middle Aged; Paclitaxel - administration & dosage; Proteomics
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1016/j.jtho.2015.11.003

Patients with advanced-stage non–small cell lung cancer (NSCLC) and borderline performance status (performance status 2 [PS2]) are often excluded from clinical trials and platinum-based therapy. In light of the potential role for serum proteomics in predicting the benefit of erlotinib beyond that of epidermal growth factor receptor gene (EGFR) mutational status, we conducted a trial in which the Veristrat proteomics assay was used for data enrichment when selecting a cohort of patients with NSCLC and PS2 to receive erlotinib with and without chemotherapy. Patients with metastatic NSCLC, PS2, acceptable end-organ function, and Veristrat-good status were randomly assigned to receive either 150 mg of erlotinib orally daily (arm 1) or 150 mg of erlotinib orally daily on days 2 through16 plus four cycles of carboplatin (area under the curve = 5 on day 1) and paclitaxel (200 mg/m2 intravenously on day 1) followed by 150 mg of erlotinib orally (arm 2). The arm 2 agents were pharmacodynamically separated to mitigate potential antagonism. The arm with superior observed median progression-free survival (PFS) would be selected for further evaluation, but only if PFS lasted for at least 3 months. The trial terminated before the planned accrual of 98 patients for regulatory reasons. A total of 156 patients were screened. Of the 83 (59%) who were classified as Veristrat good, 59 met the trial eligibility criteria and were randomly assigned to one of two arms (33 patients in arm 1 and 26 in arm 2). The patients in arm 2 patients had a higher response rate (23% versus 6%, p = 0.06), disease control rate (77% versus 41%, p = 0.0046), median PFS (4.6 versus 1.6 months, p = 0.06), and median overall survival (11 versus 6 months, p = 0.27). Treatment-related grade 4 adverse events were seen in two patients in arm 1 (thrombosis and hypomagnesemia) and in five patients in arm 2 (neutropenia in five, febrile neutropenia in one, and leukopenia in one). In a proteomics-enriched cohort of patients with NSCLC and PS2, pharmacodynamically separated erlotinib plus chemotherapy had better efficacy than did erlotinib alone and surpassed the protocol-specified benchmark of PFS of at least 3 months required for further study.