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.

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.

• Authors: 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
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 29 Issue 19 Pg. 2667-74 (Jul 01 2011) ISSN: 1527-7755 [Electronic] United States
• PMID: 21632509 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Oligodeoxyribonucleotides
• ProMune
• Toll-Like Receptor 9
• Carboplatin
• Paclitaxel

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carboplatin (administration & dosage)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Disease Progression
• Female
• Humans
• Lung Neoplasms (drug therapy)
• Male
• Middle Aged
• Oligodeoxyribonucleotides (administration & dosage)
• Paclitaxel (administration & dosage)
• Toll-Like Receptor 9 (agonists)
• Treatment Outcome