A phase III randomized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung cancer
| Autor: | Petr Zatloukal, Maria Blasinska-Morawiec, Sandra J. Meech, Jacek Jassem, Nick Thatcher, Christian Manegold, Rebecca J. Benner, N. van Zandwijk, Eng Huat Tan, A. Ingrosso, Piotr Serwatowski, Maciej Krzakowski, David Robert John Readett, Aleksandra Szczesna, J. S.-K. Au |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Oncology medicine.medical_specialty Lung Neoplasms medicine.medical_treatment Kaplan-Meier Estimate Deoxycytidine Disease-Free Survival law.invention Randomized controlled trial law Carcinoma Non-Small-Cell Lung Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Clinical endpoint Humans Lung cancer Adverse effect Aged Neoplasm Staging Proportional Hazards Models Aged 80 and over Cisplatin Chemotherapy business.industry Hematology Middle Aged medicine.disease Gemcitabine Surgery Discontinuation Oligodeoxyribonucleotides Female business medicine.drug |
| Zdroj: | Annals of Oncology. 23:72-77 |
| ISSN: | 0923-7534 |
| Popis: | Background This open-label phase III study assessed the addition of Toll-like receptor 9-activating oligodeoxynucleotide PF-3512676 to gemcitabine/cisplatin chemotherapy in patients with non-small-cell lung cancer (NSCLC). Patients and methods Chemotherapy-naive patients with stage IIIB or IV NSCLC were randomized (1:1) to receive six or fewer 3-week cycles of i.v. gemcitabine (1250 mg/m2 on days 1 and 8) and cisplatin alone (75 mg/m2 on day 1, control arm) or combined with s.c. PF-3512676 0.2 mg/kg on days 8 and 15 of each chemotherapy cycle and weekly thereafter until progression or unacceptable toxicity (experimental arm). No crossover was planned. The primary end point was overall survival (OS). Results A total of 839 patients were randomized. Baseline demographics were well balanced. Median OS (11.0 versus 10.7 months; P = 0.98) and median progression-free survival (PFS) (both 5.1 months) were similar between groups. Grade ≥3 hematologic adverse events (AEs), injection-site reactions, and influenza-like symptoms were more frequently reported among patients receiving PF-3512676. At the first-interim analysis, the Data Safety Monitoring Committee recommended study discontinuation. Administration of PF-3512676 was halted based on efficacy futility and increased grade ≥3 AEs (experimental arm). Conclusions Addition of PF-3512676 to gemcitabine/cisplatin chemotherapy did not improve OS or PFS but did increase toxicity. |
| Databáze: | OpenAIRE |
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