Levi Garraway, MD, PhD
Adding ramucirumab (Cyramza) to cisplatin and capecitabine or 5-FU (5-fluorouracil) in the frontline setting did not improve overall survival (OS) in patients with HER2-negative metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, according to topline results from the phase III RAINFALL trial.
The study did meet the primary endpoint of improved progression-free survival (PFS), according to Eli Lilly and Company, the manufacturer of the VEGFR-2 inhibitor. Lilly plans to present the results at a future medical meeting.
"While we hoped that the positive PFS outcome would have translated into an OS benefit, these RAINFALL results highlight the challenges associated with improving outcomes for people with advanced gastric cancer," Levi Garraway, MD, PhD, senior vice president, global development and medical affairs, Lilly Oncology, said in a statement.
"This is underscored by the fact that there have been no major advances over standard chemotherapy in the first-line HER2-negative gastric cancer treatment setting in the last decade,” added Garraway.
RAINFALL is a global, randomized, double-blinded, placebo-controlled phase III study of ramucirumab in combination with cisplatin and capecitabine as a first-line treatment in patients with metastatic gastric or GEJ adenocarcinoma. Study participants unable to take capecitabine (tablets) were given 5-fluorouracil (5-FU).
Overall 645 patients were randomized to either the ramucirumab regimen or chemotherapy alone. The study began in 2015 and enrolled patient in 19 countries in North America, Asia (Japan), Europe, and Latin America.
There were no new safety signals with ramucirumab. Grade ≥3 adverse events reported in at least 5% of the ramucirumab arm and occurring at a higher incidence than in the control arm included hypertension, hand-foot syndrome, and fatigue.
In April 2014, the FDA approved ramucirumab as a treatment for patients with unresectable gastric cancer or GEJ adenocarcinoma following fluoropyrimidine- or platinum-containing therapy, based on a significant extension in OS.
The approval was based on the phase III REGARD study, in which 355 patients with advanced gastric cancer or GEJ adenocarcinoma were randomized 2:1 to receive best supportive care plus either ramucirumab (n = 238) or placebo (n = 117).
The median OS was 5.2 months with ramucirumab versus 3.8 months with placebo (HR, 0.776; 95% CI, 0.603-0.998; P
= .047). The median PFS was 2.1 versus 1.3 months, respectively (HR, 0.483; 95% CI, 0.376-0.620; P
In November 2014, the FDA has approved the combination of ramucirumab and paclitaxel as a treatment for patients with previously treated advanced gastric or GEJ adenocarcinoma, based on data from the phase III RAINBOW trial.
In the RAINBOW trial, 665 patients with GEJ and gastric adenocarcinoma were evenly randomized to receive ramucirumab plus paclitaxel (n = 330) or placebo plus paclitaxel (n = 335). In the study, the median OS was 9.6 months with ramucirumab plus paclitaxel versus 7.4 months for paclitaxel alone (HR, 0.81; 95% CI, 0.678-0.962; P
= .017). The median PFS was 4.4 versus 2.9 months, for the ramucirumab and placebo arms, respectively (HR, 0.64; 95% CI, 0.536-0.752; P