Adding Bevacizumab to Perioperative Chemotherapy in Esophagogastric Adenocarcinoma
In the UK Medical Research Council ST03 phase II/III trial reported in The Lancet Oncology, Cunningham et al found that adding bevacizumab (Avastin) to perioperative chemotherapy did not improve survival in patients with operable esophagogastric cancer and may have been associated with impaired wound healing.
Study Details
In the open-label trial, 1,063 patients with resectable gastric, esophagogastric junction, or lower esophageal adenocarcinoma from 87 UK sites were randomized between October 2007 and March 2014 to receive chemotherapy plus bevacizumab (n = 530) or chemotherapy alone (n = 533). Chemotherapy consisted of 3 preoperative and 3 postoperative cycles of epirubicin at 50 mg/m² and cisplatin at 60 mg/m² on day 1 and capecitabine at 1,250 mg/m² on days 1 to 21. Bevacizumab was given as 7.5 mg/kg on day 1 of every chemotherapy cycle followed by 6 doses given once every 21 days as maintenance treatment. The primary outcome for the phase III stage of the trial was overall survival in the intention-to-treat population.
Overall Survival
A total of 1,054 patients started chemotherapy after randomization, and a total of 895 patients (84%), including 83% of the bevacizumab group and 86% of the control group, underwent resection. Median follow-up was 38.4 months.
Three-year overall survival was 48.1% (95% confidence interval [CI] = 43.2%–52.7%) in the bevacizumab group vs 50.3% (95% CI = 45.5%–54.9%) in the control group (hazard ratio [HR] = 1.08, P = .36). No evidence of a treatment effect of bevacizumab on disease-free survival (HR = 1.04, P = .62) or progression-free survival (HR = 1.05, P = .56) was observed.
Adverse Events
Neutropenia was the only grade ≥ 3 adverse event occurring in > 10% of patients in either group; it was observed in 26% of the bevacizumab group vs 27% of the control group preoperatively and in 32% vs 33% postoperatively. Postoperative wound-healing complications occurred in 12% vs 7% of patients, respectively. Among the 453 patients who underwent esophagogastrectomy, postoperative anastomotic leaks were observed in 24% vs 10% of patients; thus, recruitment of patients with lower esophageal or junctional tumors with planned esophagogastric resection was stopped toward the end of the trial. The most common serious adverse events were gastrointestinal events (63 vs 60 events), anastomotic leaks (69 vs 30 events), and infection with normal neutrophil counts (53 vs 42 events).
The investigators concluded: “The results of this trial do not provide any evidence for the use of bevacizumab in combination with peri-operative epirubicin, cisplatin, and capecitabine chemotherapy for patients with resectable gastric, oesophagogastric junction, or lower oesophageal adenocarcinoma. Bevacizumab might also be associated with impaired wound healing.”
The study was funded by Cancer Research UK, the Medical Research Council Clinical Trials Unit at University College London, and F. Hoffmann-La Roche Limited.
David Cunningham, MD, of The Royal Marsden NHS Foundation Trust, is the corresponding author of The Lancet Oncology article.
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