Randomized phase III trial of paclitaxel/carboplatin with or without PF-3512676 (toll-like receptor 9 agonist) as first-line treatment for advanced non-small-cell lung cancer

Vera Hirsh, Luis Paz-Ares, Michael Boyer, Rafael Rosell, Gary Middleton, Wilfried E.E. Eberhardt, Aleksandra Szczesna, Pavel Reiterer, Mansoor Saleh, Oscar Arrieta, Emilio Bajetta, Roy T. Webb, Johannes Raats, Rebecca J. Benner, Camilla Fowst, Sandra J. Meech, David Readett, Joan H. Schiller

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124 Citations (Scopus)

Abstract

Purpose: This phase III study examined efficacy of the synthetic Toll-like receptor 9 - activating oligodeoxynucleotide PF-3512676 in combination with standard paclitaxel/carboplatin chemotherapy in patients with advanced non - small-cell lung cancer (NSCLC). Patients and Methods: Chemotherapy-naive patients with stage IIIB or IV NSCLC were randomly assigned (1:1) to receive up to six courses of paclitaxel/carboplatin (intravenous paclitaxel 200 mg/m 2 and carboplatin at area under the [concentration-time] curve 6 on day 1 of a 3-week cycle) alone (control arm) or in combination with 0.2 mg/kg subcutaneous PF-3512676 on days 8 and 15 (investigational arm). Primary end point was overall survival (OS). Results: Baseline demographics were similar across arms (N = 828). Most patients (88%) had stage IV disease. Median OS and median progression-free survival (PFS) were similar (OS: investigational arm, 10.0 months v control arm, 9.8 months; P = .56; PFS: investigational arm, 4.8 months v control arm, 4.7 months; P = .79). Most commonly reported PF-3512676-related adverse events (AEs) were mild-to-moderate local injection site reactions, pyrexia, and flu-like symptoms. In the investigational arm, grades 3 to 4 AEs, including neutropenia, thrombocytopenia, and anemia, were more frequent, and more patients had one or more sepsis-related AEs versus controls (17 v 3). At first interim analysis, the Data Safety Monitoring Committee recommended study discontinuation because of lack of incremental efficacy and more sepsis-related serious AEs in the PF-3512676 arm. Administration of PF-3512676, but not chemotherapy, was halted. Conclusion: Addition of PF-3512676 to paclitaxel/carboplatin did not improve OS or PFS versus paclitaxel/ carboplatin alone for first-line treatment of patients with advanced NSCLC but did increase toxicity. This regimen cannot be recommended for treating patients with advanced NSCLC.

Original languageEnglish
Pages (from-to)2667-2674
Number of pages8
JournalJournal of Clinical Oncology
Volume29
Issue number19
DOIs
Publication statusPublished - 1 Jul 2011
Externally publishedYes

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