Abstract LB-67: REGARD: A phase III, randomized, double-blind trial of ramucirumab and best supportive care (BSC) versus placebo and BSC in the treatment of metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma following disease progression on first-line p
Authors: Fuchs Charles S. , Tomasek Jiri , Cho Jae Yong , Filip Dumitru , Passalacqua Rodolfo , Goswami Chancal , Safran Howard , Dos Santos Lucas Vieira , Aprile Giuseppe , Ferry David , Melichar Bohuslav , Tehfe Moustapha , Topuzov Eldar , Tabernero Josep , Zalcberg John Raymond , Chau Ian , Koshiji Minori , Hsu Yanzhi , Schwartz Jonathan , Ajani Jaffer 
Published: August 2014

Abstract
Background: VEGF and VEGF receptor-2 mediated signaling and angiogenesis may contribute to gastric cancer pathogenesis. Ramucirumab (RAM; IMC-1121B) is a fully human IgG1 monoclonal antibody targeting VEGFR-2. We conducted a placebo-controlled, double-blind, phase III international trial to evaluate the safety and efficacy of RAM in pts with metastatic gastric or GEJ adenocarcinoma progressing on 1st-line platinum- and/or fluoropyrimidine containing combination therapy.
Methods: Pts were randomized 2:1 to receive RAM (8 mg/kg IV) or placebo (PL) every 2 weeks (wks) until disease progression, unacceptable toxicity, or death. Pts had disease progression within 4 months (m) after 1st-line therapy for metastatic disease or within 6 m after adjuvant therapy. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), 12-wk PFS rate, overall response rate (ORR) and safety.
Results: From 10/09 to 01/12, 355 pts were randomized (RAM: 238; PL: 117). Baseline characteristics were well balanced between arms. RAM significantly reduced all-cause mortality by 22% when compared to PL (Hazard Ratio [HR] for OS = 0.776; 95% CI, 0.603-0.998; p = 0.0473). Median OS was 5.2 m for RAM and 3.8 m for PL. The OS benefit for RAM appeared consistent across subgroups and after adjustment for other prognostic factors (multivariate HR = 0.774; 95% CI, 0.605-0.991). The HR for PFS was 0.483 (95% CI, 0.376-0.620; p &lt; 0.0001). Median PFS was 2.1 m for RAM and 1.3 m for PL. 12-wk PFS was 40% for RAM and 16% for PL. ORR was 3.4% for RAM and 2.6% for PL. Disease control rate was 49% for RAM and 23% for PL (p &lt; 0.0001). Use of anti-cancer therapy post-study: 32% RAM; 39% PL. The most frequent grade ≥3 AEs were: hypertension (7.6% RAM; 2.6% PL), fatigue (6.4% RAM; 9.6% PL), anemia (6.4% RAM; 7.8% PL), abdominal pain (5.9% RAM; 2.6% PL), ascites (4.2% RAM; 4.3% PL), decreased appetite (3.4% RAM; 3.5% PL), bleeding (3.4% RAM; 2.6% PL), and hyponatremia (3.4% RAM; 0.9% PL).
Conclusions: Ramucirumab significantly prolonged survival in pts with advanced gastric or GE junction adenocarcinoma following progression on first-line therapy with an acceptable safety profile. These results validate VEGFR-2 signaling as a therapeutic target in gastric cancer. Clinical trial: NCT00917384
Citation Format: Charles S. Fuchs, Jiri Tomasek, Jae Yong Cho, Dumitru Filip, Rodolfo Passalacqua, Chancal Goswami, Howard Safran, Lucas Vieira Dos Santos, Giuseppe Aprile, David Ferry, Bohuslav Melichar, Moustapha Tehfe, Eldar Topuzov, Josep Tabernero, John Raymond Zalcberg, Ian Chau, Minori Koshiji, Yanzhi Hsu, Jonathan Schwartz, Jaffer Ajani. REGARD: A phase III, randomized, double-blind trial of ramucirumab and best supportive care (BSC) versus placebo and BSC in the treatment of metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma following disease progression on first-line p [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-67. doi:10.1158/1538-7445.AM2013-LB-67