Background: Vinfluine (VFL) is a new microtubule inhibitor of the vinca alkaloid class with clinical
activity in NSCLC. 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/320mg/m2, 20-min IV infusion) or DTX (75mg/m2) 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 ¾ toxicities were low in both arms:
neutropenia (33% vs. 30%), anemia (8% vs. 3%), thrombocythopenia (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%
Cl: 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.
