Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy.
OBJECTIVE
To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy.


METHODS
Randomized, multicenter, phase III study, 551 patients received either vinflunine 320 mg/m(2) or docetaxel 75 mg/m(2) every 21 days until disease progression or serious toxicity. The primary end point was progression-free survival (PFS). The noninferiority analysis was based on a 10% difference (types I/II error rates: 5%/20%). Secondary end points included response rate (ORR), response duration, overall survival (OS), clinical benefit, quality of life (QOL), and safety.


RESULTS
Median PFS was 2.3 months for each arm (HR, 1.004; 95% CI, 0.841 to 1.199). ORR, stable disease, median OS, were 4.4% versus 5.5%, 36.0% versus 39.6%, 6.7 versus 7.2 months (HR, 0.973; 95% CI, 0.805 to 1.176), respectively. No significant difference in patient benefit and QOL (Functional Assessment of Cancer Therapy-Lung). No unexpected adverse events were observed. Grade higher than 0 (vinflunine v docetaxel) anemia (82.1% v 79.8%), neutropenia (49.3 v 39.02%), thrombocytopenia (30.6% v 14.3%), febrile neutropenia (3.3% v 4.7%), constipation (39.2% v 11.7%), fatigue (36.6% v 33.9%), injection site reaction (31.9% v 0.7%), nausea (26.7% v 23.7%), vomiting (23.8% v 14.2%), alopecia (19.8% v 35.4%), stomatis (19.4% v 12.4%), abdominal pain (20.1% v 3.6%), myalgia (14.7% v 6.6%), peripheral neuropathy (10.7% v 15.0%), arthralgia (7.0% v 7.7%), diarrhea (6.2% v 12.4%), edema (1.5% v 5.4%), and nail disorders (1.1% v 5;1%) were observed.


CONCLUSIONS
This noninferiority phase III study showed similar efficacy end points for vinflunine and docetaxel. Despite higher rates of some adverse effects (anemia, abdominal pain, constipation, fatigue) the overall toxicity profile of vinflunine was manageable. Therefore, VFL may be another option in the second-line treatment of patients with advanced NSCLC.
Krzakowski
Maciej
M
Centrum Onkologii Instytut, Warsaw, Poland.
Ramlau
Rodryg
R
Jassem
Jacek
J
Szczesna
Aleksandra
A
Zatloukal
Petr
P
Von Pawel
Joachim
J
Sun
Xushan
X
Bennouna
Jaafar
J
Santoro
Armando
A
Biesma
Bonne
B
Delgado
François M
FM
Salhi
Yacine
Y
Vaissiere
Nathalie
N
Hansen
Olfred
O
Tan
Eng-Huat
EH
Quoix
Elisabeth
E
Garrido
Pilar
P
Douillard
Jean-Yves
JY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D000077143:Docetaxel; D005060:Europe; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017671:Platinum Compounds / Q000008:administration & dosage; D011788:Quality of Life; D012846:Singapore; D043823:Taxoids / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D055815:Young Adult
D017671:Platinum Compounds; D043823:Taxoids; D000077143:Docetaxel; C111217:vinflunine; D014747:Vinblastine