Phase III study of vinflunine versus docetaxel in patients (pts) with advanced non-small cell lung cancer (NSCLC) previously treated with a platinum-containing regimen

Abstract

7511 Background: Vinflunine (VFL) is a new microtubule inhibitor of the vinca alkaloid class with clinical activity in NSCLC (J. Bennouna, BJC, 2006). Single-agent efficacy and safety of VFL and docetaxel (DTX) were compared in the 2nd line chemotherapy. Methods: Open-label, multi-center, randomised, phase III study in platinum pre-treated locally advanced/metastatic NSCLC pts. At least 275 pts were to be randomized by arm to receive VFL (320 mg/m2, 20-min IV infusion) or DTX (75 mg/m2, 1-hour IV infusion with dexamethasone over 3 days) every 3 weeks. The primary endpoint was progression free survival (PFS), with a non-inferiority analysis based on a 10% difference (types I and II error rates: 5%, 20%). Results: From 06/03 to 03/05, 551 pts were randomized (VFL: 274; DTX: 277) and 547 treated (411 men, 136 women); median age 61 years [range 22–83]; ECOG PS 0–1: 89%; metastatic: 90%. All pts were platinum pre-treated, in combination with a vinca alkaloid (22%), paclitaxel (21%), or gemcitabine (48%). A total of 950 [1–20] and 1,025 [1–18] cycles were given with VFL and DTX respectively. Grade 3/4 toxicities were low in both arms: neutropenia (33% vs 30%), anemia (8% vs 3%), thrombocytopenia (2% vs <1%), febrile neutropenia (3% vs 5%), fatigue (11% vs 6%), vomiting (2% vs 1%), abdominal pain (4% vs <1%), constipation (7% vs <1%). Overall incidence of alopecia was: 20% vs 35%, nail disorders 1% vs 6%, injection site reaction 25% vs 1%, peripheral neuropathy 11% vs 15%, diarrhea 6% vs 12%. Efficacy: All efficacy endpoints were similar: median PFS (2.3 vs 2.3 months, HR:1.004 [95% CI: 0.841–1.199]), independent review response rate (4.4% vs 5.5%), stable disease (36.0% vs 39.6%), disease control (40.4 vs 45.1), median overall survival (6.7 vs 7.2 months, HR: 0.973 [0.805–1.176]). Conclusion: VFL shows efficacy equivalent to docetaxel in 2nd line NSCLC chemotherapy. Low, manageable but different toxicity profiles were observed in either arm. Vinflunine offers a new and useful alternative for the 2nd line treatment of pts with this disease. No significant financial relationships to disclose.