TY - JOUR
T1 - 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
AU - Hirsh, Vera
AU - Paz-Ares, Luis
AU - Boyer, Michael
AU - Rosell, Rafael
AU - Middleton, Gary
AU - Eberhardt, Wilfried E E
AU - Szczesna, Aleksandra
AU - Reiterer, Pavel
AU - Saleh, Mansoor
AU - Arrieta, Oscar
AU - Bajetta, Emilio
AU - Webb, Roy T.
AU - Raats, Johannes
AU - Benner, Rebecca J.
AU - Fowst, Camilla
AU - Meech, Sandra J.
AU - Readett, David
AU - Schiller, Joan H.
PY - 2011/7/1
Y1 - 2011/7/1
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2010.32.8971
DO - 10.1200/JCO.2010.32.8971
M3 - Article
C2 - 21632509
AN - SCOPUS:79960110662
SN - 0732-183X
VL - 29
SP - 2667
EP - 2674
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 19
ER -