PMID- 29373274 OWN - NLM STAT- MEDLINE DCOM- 20190308 LR - 20231213 IS - 1938-0690 (Electronic) IS - 1525-7304 (Linking) VI - 19 IP - 3 DP - 2018 May TI - Efficacy and Safety of Ramucirumab With Docetaxel Versus Placebo With Docetaxel as Second-Line Treatment of Advanced Non-Small-Cell Lung Cancer: A Subgroup Analysis According to Patient Age in the REVEL Trial. PG - 270-279.e3 LID - S1525-7304(17)30350-9 [pii] LID - 10.1016/j.cllc.2017.12.011 [doi] AB - INTRODUCTION: Ramucirumab, a recombinant human immunoglobulin G1 monoclonal antibody receptor antagonist designed to block the ligand-binding site of vascular endothelial growth factor receptor-2 (VEGFR-2), was evaluated as second-line treatment in combination with docetaxel in patients with non-small-cell lung cancer in the REVEL trial (NCT01168973). Ramucirumab significantly improved overall survival (OS) and progression-free survival (PFS). We report age subgroup analysis results primarily on the basis of a 65-year cutoff. PATIENTS AND METHODS: Patients were randomized 1:1 to ramucirumab with docetaxel or placebo with docetaxel (n = 1253). Of these, 798 were younger than 65 years (ramucirumab, n = 391; control, n = 407) and 455 were 65 years or older (ramucirumab, n = 237; control, n = 218). Treatment comprised 21-day cycles of 75 mg/m(2) docetaxel with 10 mg/kg ramucirumab or placebo. Prespecified age subgroup analyses were performed, including OS, PFS, and objective response rate. Quintiles age analysis was conducted to establish a relationship between efficacy and age. The Lung Cancer Symptom Scale (LCSS) measured quality of life outcomes. Safety was assessed according to adverse events (AEs). RESULTS: Patients younger than 65 years showed favorable OS outcomes with ramucirumab treatment (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.62-0.87; P < .001) and PFS (HR, 0.68; 95% CI, 0.59-0.79; P < .001). In patients 65 years or older, benefits of ramucirumab were not as evident; after model adjustment for prognostic factors, OS and PFS HRs were 0.96 (95% CI, 0.77-1.21; P = .04) and 0.87 (95% CI, 0.71-1.05; P = .03), respectively. Age analysis according to quintiles showed HRs favoring ramucirumab for all age groupings. LCSS scores and AEs did not considerably differ between age groups. CONCLUSION: In this subgroup analysis, true treatment effect differences on the basis of age have not been established, and treatment should not be deterred solely because of age. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Ramalingam, Suresh S AU - Ramalingam SS AD - Emory University School of Medicine, Winship Cancer Institute of Emory University, Clifton Campus, Atlanta, GA. Electronic address: ssramal@emory.edu. FAU - Perol, Maurice AU - Perol M AD - Department of Medical Oncology, Leon Berard Cancer Center, Lyon, France. FAU - Reck, Martin AU - Reck M AD - LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Wohrendamm, Grosshansdorf, Germany. FAU - Kowalyszyn, Ruben Dario AU - Kowalyszyn RD AD - Centro de Investigaciones Clinicas, Instituto Multidisciplinario de Oncologia, Clinica Viedma, Rio Negro, Argentina. FAU - Gautschi, Oliver AU - Gautschi O AD - Luzemer Kantonsspital, Luzern, Switzerland. FAU - Kimmich, Martin AU - Kimmich M AD - Klinik Schillerhohe, Gerlingen, Germany. FAU - Cho, Eun Kyung AU - Cho EK AD - Hematology-Oncology Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, South Korea. FAU - Czyzewicz, Grzegorz AU - Czyzewicz G AD - Department of Chemotherapy, John Paul II Hospital, Krakow, Poland. FAU - Grigorescu, Alexandru AU - Grigorescu A AD - Department of Medical Oncology, Institute of Oncology, Bucharest, Romania. FAU - Karaseva, Nina AU - Karaseva N AD - City Clinical Oncology Dispensary, St Petersburg, Russian Federation. FAU - Dakhil, Shaker AU - Dakhil S AD - Cancer Center of Kansas, Wichita, KS. FAU - Lee, Pablo AU - Lee P AD - Eli Lilly and Company, Indianapolis, IN. FAU - Zimmerman, Annamaria AU - Zimmerman A AD - Eli Lilly and Company, Indianapolis, IN. FAU - Sashegyi, Andreas AU - Sashegyi A AD - Eli Lilly and Company, Indianapolis, IN. FAU - Alexandris, Ekaterine AU - Alexandris E AD - Eli Lilly and Company, Indianapolis, IN. FAU - Carter, Gebra Cuyun AU - Carter GC AD - Eli Lilly and Company, Indianapolis, IN. FAU - Winfree, Katherine B AU - Winfree KB AD - Eli Lilly and Company, Indianapolis, IN. FAU - Garon, Edward B AU - Garon EB AD - David Geffen School of Medicine at UCLA/TRIO-US Network, Los Angeles, CA. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20171221 PL - United States TA - Clin Lung Cancer JT - Clinical lung cancer JID - 100893225 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 15H5577CQD (Docetaxel) RN - EC 2.7.10.1 (KDR protein, human) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2) SB - IM MH - Adult MH - Age Factors MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal/*administration & dosage/adverse effects MH - Antibodies, Monoclonal, Humanized MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/mortality MH - Docetaxel/administration & dosage/adverse effects MH - Double-Blind Method MH - Female MH - Humans MH - Kaplan-Meier Estimate MH - Lung Neoplasms/*drug therapy/mortality MH - Male MH - Middle Aged MH - Salvage Therapy/methods MH - Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors MH - Young Adult MH - Ramucirumab OTO - NOTNLM OT - Angiogenesis OT - Elderly OT - NSCLC OT - Phase 3 OT - VEGF EDAT- 2018/01/27 06:00 MHDA- 2019/03/09 06:00 CRDT- 2018/01/27 06:00 PHST- 2017/06/06 00:00 [received] PHST- 2017/11/30 00:00 [revised] PHST- 2017/12/17 00:00 [accepted] PHST- 2018/01/27 06:00 [pubmed] PHST- 2019/03/09 06:00 [medline] PHST- 2018/01/27 06:00 [entrez] AID - S1525-7304(17)30350-9 [pii] AID - 10.1016/j.cllc.2017.12.011 [doi] PST - ppublish SO - Clin Lung Cancer. 2018 May;19(3):270-279.e3. doi: 10.1016/j.cllc.2017.12.011. Epub 2017 Dec 21.