Josep Tabernero, MD, PhD
Ramucirumab, a novel monoclonal antibody that targets vascular epithelial growth factor receptor-2 (VEGFR-2), significantly prolongs survival in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma following progression on first-line therapy—the first single biologic agent to do so, according to a randomized phase III study presented July 4, 2013 at the European Society for Medical Oncology 15th World Congress on Gastrointestinal Cancer in Barcelona, Spain.
Joseph Tabernero, MD, PhD, of Vall d’Hebron University Hospital, Barcelona, and multicenter colleagues in the REGARD trial found that ramucirumab significantly prolonged overall survival (OS) by 22% (P
= .0473) as well as progression-free survival (PFS) by 52% (P
<.0001) compared with placebo in patients with metastatic gastric or GEJ adenocarcinoma following progression on first-line platinum or fluoropyrimidine-containing regimens or both.
“These results confirm VEGFR-2 as a viable therapeutic target in gastric cancer,” Tabernero said, “and ramucirumab represents a potential new second-line standard of care in this patient population.”
For the study, 355 patients were randomized to either ramucirumab (8 mg/kg IV) or placebo, given every 2 weeks until disease progression or intolerable toxicity. Approximately two-thirds of patients were >65 years of age at randomization. The primary tumor was gastric in approximately75% of patients, the remainder being at the GE junction. A significant proportion of patients in both arms also had three or more metastatic sites prior to randomization.
Few to no patients achieved a complete response (CR) but 2.9% of ramucirumab patients achieved a partial response (PR) as did 2.6% of placebo patients. Disease stabilized in more than twice as many patients in the active therapy arm (~45%) compared with approximately 20% among placebo controls. Disease control (CR plus PR plus stable disease) was also achieved in almost half of patients on active therapy versus 23% for controls (P
Tabernero reported that median OS was 5.2 months for patients receiving ramucirumab compared with 3.8 months for placebo. At 6 months, 42% of patients on ramucirumab were still alive compared with 32% of placebo controls. At 12 months, 18% and 12% of patients were alive on active versus control therapy, respectively. The median interlude before patients progressed was 2.1 months for the ramucirumab arm compared with 1.3 months for placebo, Tabernero added.
At 12 weeks, 40% of patients on active treatment still had not progressed compared with only 10% of placebo patients. Both the OS and the PFS benefit seen with the VEGFR-2 inhibitor appeared consistent across all subgroups analyzed and after adjustment for other prognostic factors. Following discontinuation of treatment in REGARD, 29% of patients formerly treated with ramucirumab went on to chemotherapy compared with approximately 37% of those formerly on placebo.
Overall, investigators felt that ramucirumab had an acceptable safety profile. Rates of grades 3 and 4 fatigue and anemia were 6.4% for each event in patients on active therapy, but these events were more common among placebo patients (9.6% and 7.8%, respectively). Rates of hypertension and bleeding or hemorrhage were higher for those receiving active therapy, but no specific treatment effects were seen in >10% of patients on active therapy.
Tabernero J, et al. REGARD phase III, randomized trial of ramucirumab in patients with metastatic gastric or GEJ adenocarcinoma following progression on first-line chemotherapy. Presented at: ESMO 15th World Congress on Gastrointestinal Cancer; July 3-6, 2013; Abstract 0-0008.
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