title: A randomized, double-blind, phase II study of ramucirumab plus docetaxel vs placebo plus docetaxel in Japanese patients with stage IV non-small cell lung cancer after disease progression on platinum-based therapy.
abstract: Ramucirumab plus docetaxel prolongs survival in patients with non-small cell lung cancer (NSCLC) with disease progression after platinum-based therapy. This phase II, double-blind, randomized, placebo-controlled study assessed efficacy and safety of second-line ramucirumab-docetaxel in Japanese patients with NSCLC.
  
  
  
  Patients with NSCLC with progression after platinum-based therapy (28 Japanese sites; 19 December, 2012 to 22 May, 2015) were randomized (computer-generated sequence) to ramucirumab 10mg/kg or placebo, followed by docetaxel 60mg/m(2) (Day 1, 21-day cycle). Prior epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) monotherapy was prohibited in the primary population, but EGFR mutation-positive NSCLC patients who were treated with EGFR-TKI were enrolled as a separate exploratory population. Primary endpoint was progression-free survival (PFS); secondary outcomes included overall survival, tumor response rates, and safety. Investigator tumor assessments were used for the efficacy endpoints.
  
  
  
  In the primary population (N=160 randomized, n=157 treated), median (95% CI) PFS was longer with ramucirumab-docetaxel (5.22 [3.52-6.97] months; n=76) than with placebo-docetaxel (4.21 [2.83-5.62] months; n=81); hazard ratio 0.83 (95% CI 0.59-1.16). Median (95% CI) overall survival was 15.15 (12.45-26.55) months with ramucirumab-docetaxel and 14.65 (11.93-24.44) months with placebo-docetaxel (hazard ratio [95% CI] 0.86 [0.56-1.32]). Objective response rate (28.9% vs 18.5%) and disease control rate (78.9% vs 70.4%) were numerically greater with ramucirumab-docetaxel than with placebo-docetaxel. Incidence and severity of most adverse events were similar, but febrile neutropenia was more common with ramucirumab-docetaxel (34.2%) than with placebo-docetaxel (19.8%).
  
  
  
  Second-line ramucirumab-docetaxel improved PFS similar to that seen in the REVEL trial with a manageable safety profile in Japanese patients with NSCLC.
authors: Department of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan. Electronic address: kyoh@east.ncc.go.jp.
authors: Kiyotaka
authors: K
authors: Yoh
authors: Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan.
authors: Yukio
authors: Y
authors: Hosomi
authors: Department of Respiratory Medicine, Kanazawa University Hospital, Kanazawa, Japan.
authors: Kazuo
authors: K
authors: Kasahara
authors: Department of Internal Medicine, Kurume University Hospital, Fukuoka, Japan.
authors: Kazuhiko
authors: K
authors: Yamada
authors: Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors: Toshiaki
authors: T
authors: Takahashi
authors: Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
authors: Nobuyuki
authors: N
authors: Yamamoto
authors: Department of Thoracic Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
authors: Makoto
authors: M
authors: Nishio
authors: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors: Yuichiro
authors: Y
authors: Ohe
authors: Eli Lilly Japan, Kobe, Japan.
authors: Toshiko
authors: T
authors: Koue
authors: Eli Lilly Japan, Kobe, Japan.
authors: Takashi
authors: T
authors: Nakamura
authors: Eli Lilly Japan, Kobe, Japan.
authors: Sotaro
authors: S
authors: Enatsu
authors: Eli Lilly and Company, Indianapolis, IN, USA.
authors: Pablo
authors: P
authors: Lee
authors: Eli Lilly and Company, Indianapolis, IN, USA.
authors: David
authors: D
authors: Ferry
authors: Thoracic Center, St. Luke's International Hospital, Tokyo, Japan.
authors: Tomohide
authors: T
authors: Tamura
authors: Department of Medical Oncology, The Faculty of Medicine, Kinki University, Osaka, Japan.
authors: Kazuhiko
authors: K
authors: Nakagawa
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D018450:Disease Progression; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010984:Platinum / Q000008:administration & dosage; D019233:Retreatment; D012307:Risk Factors; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome; D000096662:Ramucirumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000077143:Docetaxel; D010984:Platinum; D043823:Taxoids; D000096662:Ramucirumab
keywords: Docetaxel; Japan; Non-small-cell lung cancer; Ramucirumab; Randomized phase II trial