Τίτλος:
Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line
treatment of stage IV non-small-cell lung cancer after disease
progression on platinum-based therapy (REVEL): a multicentre,
double-blind, randomised phase 3 trial
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background Ramucirumab is a human IgG1 monoclonal antibody that targets
the extracellular domain of VEGFR-2. We aimed to assess efficacy and
safety of treatment with docetaxel plus ramucirumab or placebo as
second-line treatment for patients with stage IV non-small-cell-lung
cancer (NSCLC) after platinum-based therapy.
Methods In this multicentre, double-blind, randomised phase 3 trial
(REVEL), we enrolled patients with squamous or non-squamous NSCLC who
had progressed during or after a first-line platinum-based chemotherapy
regimen. Patients were randomly allocated (1:1) with a centralised,
interactive voice-response system (stratified by sex, region,
performance status, and previous maintenance therapy [yes vs no]) to
receive docetaxel 75 mg/m(2) and either ramucirumab (10 mg/kg) or
placebo on day 1 of a 21 day cycle until disease progression,
unacceptable toxicity, withdrawal, or death. The primary endpoint was
overall survival in all patients allocated to treatment. We assessed
adverse events according to treatment received. This study is registered
with ClinicalTrials.gov, number NCT01168973.
Findings Between Dec 3, 2010, and Jan 24, 2013, we screened 1825
patients, of whom 1253 patients were randomly allocated to treatment.
Median overall survival was 10.5 months (IQR 5.1-21.2) for 628 patients
allocated ramucirumab plus docetaxel and 9.1 months (4.2-18.0) for 625
patients who received placebo plus docetaxel (hazard ratio 0.86, 95% CI
0.75-0.98; p=0.023). Median progression-free survival was 4.5 months
(IQR 2.3-8.3) for the ramucirumab group compared with 3.0 months
(1.4-6.9) for the control group (0.76, 0.68-0.86; p<0.0001). We noted
treatment-emergent adverse events in 613 (98%) of 627 patients in the
ramucirumab safety population and 594 (95%) of 618 patients in the
control safety population. The most common grade 3 or worse adverse
events were neutropenia (306 patients [49%] in the ramucirumab group
vs 246 [40%] in the control group), febrile neutropenia (100 [16%]
vs 62 [10%]), fatigue (88 [14%] vs 65 [10%]), leucopenia (86
[14%] vs 77 [12%]), and hypertension (35 [6%] vs 13 [2%]).
The numbers of deaths from adverse events (31 [5%] vs 35 [6%]) and
grade 3 or worse pulmonary haemorrhage (eight [1%] vs eight [1%])
did not differ between groups. Toxicities were manageable with
appropriate dose reductions and supportive care.
Interpretation Ramucirumab plus docetaxel improves survival as
second-line treatment of patients with stage IV NSCLC.
Συγγραφείς:
Garon, Edward B.
Ciuleanu, Tudor-Eliade
Arrieta, Oscar and
Prabhash, Kumar
Syrigos, Konstantinos N.
Goksel, Tuncay and
Park, Keunchil
Gorbunova, Vera
Dario Kowalyszyn, Ruben and
Pikiel, Joanna
Czyzewicz, Grzegorz
Orlov, Sergey V. and
Lewanski, Conrad R.
Thomas, Michael
Bidoli, Paolo
Dakhil,
Shaker
Gans, Steven
Kim, Joo-Hang
Grigorescu, Alexandru and
Karaseva, Nina
Reck, Martin
Cappuzzo, Federico
Alexandris,
Ekaterine
Sashegyi, Andreas
Yurasov, Sergey
Perol, Maurice
Περιοδικό:
The Lancet Neurology
Εκδότης:
EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
DOI:
10.1016/S0140-6736(14)60845-X
