Kiyotaka Yoh1, Yukio Hosomi2, Kazuo Kasahara3, Kazuhiko Yamada4, Toshiaki Takahashi5, Nobuyuki Yamamoto6, Makoto Nishio7, Yuichiro Ohe8, Toshiko Koue9, Takashi Nakamura9, Sotaro Enatsu9, Pablo Lee10, David Ferry10, Tomohide Tamura11, Kazuhiko Nakagawa12. 1. Department of Thoracic Oncology, National Cancer Center Hospital East, Chiba, Japan. Electronic address: kyoh@east.ncc.go.jp. 2. Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. 3. Department of Respiratory Medicine, Kanazawa University Hospital, Kanazawa, Japan. 4. Department of Internal Medicine, Kurume University Hospital, Fukuoka, Japan. 5. Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan. 6. Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan. 7. Department of Thoracic Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan. 8. Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. 9. Eli Lilly Japan, Kobe, Japan. 10. Eli Lilly and Company, Indianapolis, IN, USA. 11. Thoracic Center, St. Luke's International Hospital, Tokyo, Japan. 12. Department of Medical Oncology, The Faculty of Medicine, Kinki University, Osaka, Japan.
Abstract
OBJECTIVES: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. MATERIALS AND METHODS: 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. RESULTS: 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%). CONCLUSION:Second-line ramucirumab-docetaxel improved PFS similar to that seen in the REVEL trial with a manageable safety profile in Japanese patients with NSCLC.
RCT Entities:
OBJECTIVES: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. MATERIALS AND METHODS: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 NSCLCpatients 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. RESULTS: 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%). CONCLUSION: 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: Manuel Cobo; Vanesa Gutiérrez; Rosa Villatoro; Jose Manuel Trigo; Inmaculada Ramos; Omar López; María Ruiz; Ana Godoy; Irene López; Macarena Arroyo Journal: Lung Cancer (Auckl) Date: 2017-07-12