New Antibody Targeting VEGF Receptor-2 Extends Survival in Advanced Gastric Cancer

Mark Knight

February 2013, Vol 4, No 2 - GI Cancers Symposium

San Francisco, CA—Ramucirumab as a second-line therapy extended overall and progression-free survival in a phase 3 clinical trial of patients with metastatic gastric cancer, said Charles S. Fuchs, MD, MPH, Director of the Center for Gastrointestinal Cancer at Dana-Farber Cancer Institute, Boston, and Professor of Medicine at Harvard Medical School, at the 2013 Gastrointestinal Cancers Symposium.

Patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma that progressed with first-line therapy who were randomized to ramuciru­mab plus best supportive care had a median 1.4 months longer overall survival (OS) than patients assigned to placebo plus best supportive care.

Ramucirumab is a fully human monoclonal antibody that targets the vascular endothelial growth factor (VEGF) receptor-2. By binding the extracellular domain of the VEGF receptor-2, it blocks the binding of VEGF ligands and inhibiting receptor activation.

The advantage in OS with ramucirumab mirrors the advantage achieved with docetaxel or irinotecan as salvage chemotherapy compared with placebo in patients with pretreated gastric cancer (Kang JH, et al. J Clin Oncol. 2012;30:1513-1518).

“The relative benefit of the antibody is very comparable to what has been achieved with chemotherapy, to the extent that it can achieve a similar benefit to second-line chemotherapy, and it has an excellent tolerability profile, which makes it an exciting option for patients,” said Dr Fuchs.

Conducted in 30 countries, the study included 355 patients with meta­static gastric or GEJ adenocarcinoma whose disease progressed within 4 months after first-line platinum- and/or fluoropyrimidine-containing combination chemotherapy or within 6 months after adjuvant therapy.

The patients were randomized in a 2:1 ratio to infusions of ramucirumab every 2 weeks plus best supportive care or to placebo infusions plus best supportive care, and were treated until disease progression or intoler­able toxicity was reached. The median duration of therapy was 8 months in the ramucirumab arm and 6 months in the placebo arm.

Median OS was 5.2 months with ramucirumab versus 3.8 months in placebo recipients, corresponding to a hazard ratio of 0.77 (P = .047).

The median time to disease progression favored ramucirumab over placebo (2.1 months vs 1.3 months, respectively).

At 6 months, OS was 42% in the ramucirumab arm versus 32% in the placebo arm, and at 12 months, OS was 18% in the ramucirumab arm versus 11% in the placebo arm.

The disease control rate, defined as complete remission, partial remission, or stable disease, was 48.7% in the ramucirumab recipients versus 23.1% in the placebo recipients (P <.001). The rates of stable disease were 45.4% in the ramucirumab arm versus 20.5% in the placebo arm.

The percentage of deaths attributed to adverse events (AEs) was similar in each arm: 10.6% versus 13.0% in the ramucirumab and the placebo arms, respectively.

No unexpected safety findings were noted, said Dr Fuchs. Fatigue was the most frequently reported AE in each study arm (35.6%, ramucirumab; 40.0%, placebo). Hypertension rates were 16.1% versus 7.8% in the ramucirumab and placebo arms, respectively, and the rates of grade 3 hypertension were 7.6% with ramucirumab and 2.6% with placebo. No grade 4 hypertension was observed.

“The next logical question is what happens when you add ramuciru­mab to chemotherapy,” concluded Dr Fuchs.