Τίτλος:
Phase III, Randomized, Double-Blind, Placebo-Controlled Trial of
Gemcitabine/Cisplatin Alone or With Sorafenib for the First-Line
Treatment of Advanced, Nonsquamous Non-Small-Cell Lung Cancer
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Purpose
This trial evaluated the efficacy and safety of sorafenib plus
gemcitabine/cisplatin in chemotherapy-naive patients with unresectable
stage IIIB to IV nonsquamous non-small-cell lung cancer (NSCLC).
Patients and Methods
Between February 2007 and March 2009, 904 patients were randomly
assigned to daily sorafenib (400 mg twice a day) or matching placebo
plus gemcitabine (1,250 mg/m(2) per day on days 1 and 8) and cisplatin
(75 mg/m(2) on day 1) for up to six 21-day cycles. Because of safety
findings from the Evaluation of Sorafenib, Carboplatin and Paclitaxel
Efficacy in NSCLC (ESCAPE) trial, patients with squamous cell histology
were withdrawn from the trial in February 2008 and excluded from
analysis. The primary end point was overall survival (OS), and secondary
end points included progression-free survival (PFS) and
time-to-progression (TTP).
Results
The primary analysis population consisted of 772 patients (sorafenib,
385; placebo, 387); the two groups had similar demographic and baseline
characteristics. Median OS was similar in the sorafenib and placebo
groups (12.4 v 12.5 months; hazard ratio [HR], 0.98; P = .401). By
investigator assessment, sorafenib improved median PFS (6.0 v 5.5
months; HR, 0.83; P = .008) and TTP (6.1 v 5.5 months; HR, 0.73; P <
.001). Grade 3 to 4 drug-related adverse events more than two-fold
higher in the sorafenib group included hand-foot skin reaction (8.6% v
0.3%), fatigue (7.3% v 3.6%), rash (5.7% v 0.5%), and hypertension
(4.2% v 1.8%). No unexpected toxicities were observed.
Conclusion
This study did not meet its primary end point of improved OS when
sorafenib was added to first-line gemcitabine/cisplatin in patients with
advanced nonsquamous NSCLC. Identification of predictive biomarkers is
warranted in future trials of sorafenib. J Clin Oncol 30: 3084-3092. (C)
2012 by American Society of Clinical Oncology
Συγγραφείς:
Paz-Ares, Luis G.
Biesma, Bonne
Heigener, David
von Pawel,
Joachim
Eisen, Timothy
Bennouna, Jaafar
Zhang, Li
Liao,
Meilin
Sun, Yan
Gans, Steven
Syrigos, Kostas
Le Marie,
Etienne
Gottfried, Maya
Vansteenkiste, Johan
Alberola,
Vincente
Strauss, Uwe Phillip
Montegriffo, Elaine
Ong, Teng
Jin
Santoro, Armando
Περιοδικό:
World Journal of Clinical Oncology
Εκδότης:
AMER SOC CLINICAL ONCOLOGY 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
DOI:
10.1200/JCO.2011.39.7646
