Randomized Phase II Trial of a Toll-Like Receptor 9 Agonist Oligodeoxynucleotide, PF-3512676, in Combination With First-Line Taxane Plus Platinum Chemotherapy for Advanced-Stage Non–Small-Cell Lung Cancer

作者：Christian Manegold, Donald Gravenor, Donald Woytowitz, J. Mezger, Vera Hirsh, Gary Albert, Mohammed Al-Adhami, David Readett, Arthur Μ. Krieg, Cynthia G. Leichman · 发表于：Journal of Clinical Oncology · 年份：2008 · DOI：10.1200/jco.2007.12.5807 · 被引用次数：169 · 研究领域：Immune Response and Inflammation、Lung Cancer Research Studies、Immunotherapy and Immune Responses

PURPOSE: This study assessed the efficacy of the combination of standard taxane plus platinum chemotherapy with the synthetic Toll-like receptor 9-activating oligodeoxynucleotide PF-3512676 in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB to IV NSCLC were randomly assigned (one to two ratio) to receive four to six cycles of taxane/platinum chemotherapy alone or with 0.2 mg/kg of subcutaneous PF-3512676 on days 8 and 15 of each 3-week cycle. The primary end point was objective response rate (ORR). RESULTS: Baseline demographics were similar between treatment arms, although significantly more patients in the PF-3512676 arm had stage IV disease (85% compared with 62% in the chemotherapy-alone arm). The modified intent-to-treat analysis (n = 111) demonstrated a 38% ORR (confirmed and unconfirmed) in the PF-3512676 arm (n = 74) and 19% in the chemotherapy-alone arm (n = 37) by investigator evaluation. Blinded, independent radiologic review for 90 patients showed a similar trend in confirmed response rate (19% and 11%, respectively). Median survival was 12.3 months in the PF-3512676 arm and 6.8 months in the chemotherapy-alone arm, and 1-year survival was 50% and 33%, respectively. Mild to moderate local injection site reactions and flu-like symptoms were the most common PF-3512676-related adverse events, but grade 3/4 neutropenia, thrombocytopenia, and anemia were all reported more commonly for patients in the P...