ASCO 2014. Abstract LBA8006. REVEL: A randomized, double-blind, phase III study of docetaxel (DOC) and ramucirumab (RAM; IMC-1121B) versus DOC and placebo (PL) in the second-line treatment of stage IV non-small cell lung cancer (NSCLC) following disease progression after one prior platinum-based therapy.
Maurice Perol, Tudor-Eliade Ciuleanu, Oscar Arrieta, Kumar Prabhash, Konstantinos N. Syrigos, Tuncay Göksel, Keunchil Park, Ruben Dario Kowalyszyn, Joanna Pikiel, Grzegorz Czyzewicz, Sergey Orlov, Conrad R. Lewanski, Ekaterine Alexandris, Annamaria Zimmerman, Nadia Chouaki, William J. John, Sergey Yurasov, Edward B. Garon; Léon-Bérard Cancer Centre, Lyon, France; Prof. Dr. I. Chiricuta Institute of Oncology, Cluj County, Romania; Instituto Nacional de Cancerologia - INCAN, Mexico City, Mexico; Tata Memorial Center, Mumbai, India; Section of Medical Oncology, Department of Internal Medicine, Yale Cancer Center, Yale University School of Medicine, New Haven, CT; Ege University, School of Medicine, Izmir, Turkey; Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Centro de Investigaciones Clínicas, Clínica Viedma, S.A., Argentina; Wojewódzkie Centrum Onkologii, Gdansk, Poland; John Paul II Hospital, Krakow, Poland; Pavlov State Medical University, St. Petersburg, Russia; Charing Cross Hospital, London, United Kingdom; ImClone Systems, a wholly-owned subsidiary of Eli Lilly & Co, Bridgewater, NJ; Eli Lilly & Co., Indianapolis, IN; Eli Lilly and Company, Paris, France; David Geffen School of Medicine, University of California Los Angeles, Translational Research in Oncology-US Network, Los Angeles, CA
Background: RAM is a human IgG1 monoclonal antibody that targets the extracellular domain of VEGFR-2. The REVEL study evaluated the efficacy and safety of RAM+DOC vs. PL+DOC (DOC) in patients (pts) with stage IV nonsquamous (NSQ) and squamous (SQ) NSCLC after platinum-based therapy.
Methods: Pts with NSQ and SQ stage IV NSCLC were randomized 1:1 (stratified by sex, region, ECOG PS, and prior maintenance therapy) to receive DOC 75 mg/m2 in combination with either RAM 10 mg/kg or PL on day 1 of a 21-day cycle until disease progression, unacceptable toxicity, or death. The primary endpoint was overall survival (OS). Secondary efficacy endpoints included progression-free survival (PFS), and objective response rate (ORR).
Results: Between Dec 2010 and Feb 2013, 1,253 pts (26.2% SQ) were randomized (RAM+DOC: 628; DOC: 625). Pt characteristics were balanced between arms. ORR was 22.9% for RAM+DOC and 13.6% for DOC (P<0.001). The hazard ratio (HR) for PFS was 0.762 (P<0.0001); median PFS was 4.5 months (m) for RAM+DOC vs. 3.0m for DOC. REVEL met its primary endpoint; the OS HR was 0.857 (95% CI 0.751, 0.98; P=0.0235); median OS was 10.5m for RAM+DOC vs. 9.1m for DOC. OS was longer for RAM+DOC in most pt subgroups, including SQ and NSQ histology. Grade ≥3 adverse events (AEs) occurring in >5% of pts on RAM+DOC were neutropenia (34.9% vs. 28.0%), febrile neutropenia (15.9% vs. 10.0%), fatigue (11.3% vs. 8.1%), leukopenia (8.5% vs. 7.6%), hypertension (5.4% vs. 1.9%), and pneumonia (5.1% vs. 5.8%). Grade 5 AEs were comparable between arms (5.4% vs. 5.8%), as was pulmonary hemorrhage (any grade; all pts: 2.1% vs. 1.6%; SQ pts: 3.8% vs. 2.4%).
Conclusions: REVEL demonstrated a statistically significant improvement in ORR, PFS, and OS for RAM+DOC vs DOC in NSCLC pts with stage IV NSCLC as second-line treatment after platinum-based therapy. Benefits were similar in NSQ and SQ pts, and no unexpected AEs were identified. Clinical trial information: NCT01168973.
- Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. Sandler A et al. Paclitaxel-carboplatin alone or with bevacizumab for non–small-cell lung cancer. N
Engl J Med. 2006;355(24):2542-2550
- Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL). Reck M et al. Ann Oncol. 2010 Sep;21(9):1804-9.
- REVEL: A randomized, double-blind, phase III study of docetaxel (DOC) and ramucirumab (RAM; IMC-1121B) versus DOC and placebo (PL) in the second-line treatment of stage IV non-small cell lung cancer (NSCLC) following disease progression after one prior platinum-based therapy. M Perol et al. J Clin Oncol 32:5s, 2014 (suppl; abstr LBA8006^)