Bevacizumab may improve surgical outcomes in advanced gastric cancer

Last Updated: 2015-11-25

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - Bevacizumab may help improve surgical outcomes in locally advanced gastric cancer (LAGC), new research from China suggests.

Adding bevacizumab to neoadjuvant docetaxel/oxaliplatin/5-fluorouracil/calcium folinate (DOF) can improve the curative (R0) surgery resection rate and disease-free survival (DFS), and these effects might be associated with lower circulating tumor cell counts, the study authors wrote.

"This is a very promising study with some exciting findings. The first is that they found circulating tumor cells (CTCs) present in 92.5% to 95% of patients with advanced gastric cancer. This confirms that advanced gastric cancer represents a systemic disease early and supports the use of chemotherapy in its treatment," Dr. Eva Galka of the Wilmot Cancer Institute of the University of Rochester Medical Center in Rochester, in New York, told Reuters Health by email.

"This study showed a significant reduction in the CTC level with the addition of bevacizumab and that this reduction was an independent prognostic factor for survival. It also showed a significant improvement in R0 and D2 (lymphadenectomy) resection in the bevacizumab group, both of which are markers of adequate surgery. The DFS, but not the OS (overall survival), improved," added Dr. Galka, who was not involved in the study.

Lead author Dr. Junxun Ma and colleagues from the Chinese People's Liberation Army General Hospital in Beijing randomized 80 LAGC patients to receive DOF with or without neoadjuvant bevacizumab. The researchers used fluorescence in situ hybridization (FISH) to count CTCs, according to an article online October 23 in Medicine.

The same team performed all surgeries, and pathologic complete remission was confirmed if the resected sample had no tumor or had only in situ lesions.

The average age was in the mid-fifties; the average length of follow-up was three years.

The bevacizumab group showed a significantly greater CTC drop after neoadjuvant therapy compared with the DOF-alone group (p=0.0335).

In addition, adding bevacizumab significantly increased the rate of R0 resections (75% vs 50%, P=0.0209) and D2 resections (77.5% vs 52.5%, P=0.0191). D2 resections are the more-extensive lymphadenectomies that are standard in regions where the incidence of gastric cancer is high.

The group receiving bevacizumab had a significantly higher total response rate (complete and partial remission) than the group receiving DOF alone (65% vs 42.5%; p=0.0436).

The bevacizumab group also had significantly improved DFS (15.2 vs 12.3 months; p=0.013), but the two groups did not differ significantly in OS (17.6 vs 16.4; p=0.776).

"The high percentage of CTC is somewhat surprising and daunting," Dr. Galka said. "We've recognized that advanced gastric cancer has a high recurrence rate even with appropriate surgery. These CTCs may be the reason for recurrences. Showing CTC count improvement and correlating this with DFS improvement is interesting."

Dr. Galka added that showing improvements in OS in such a small study is difficult and that it's unclear whether DFS improvements are a surrogate for OS improvements.

"DOF is an aggressive first-line regimen for gastric cancer and comes with many toxicities, but this was not addressed in the study. I would like to have seen the toxicity profile and percentage of patients who completed the regimen," she said.

"The results of this small trial in a Chinese population would need to be reproduced in a larger multicenter trial," Dr. Galka advised. "Historical studies have shown differences in outcomes in western versus Asian populations in gastric cancer, and there may truly be a difference between gastric cancer in the East and gastric cancer in the West. I would like to see this study repeated in an international setting."

Dr. Timothy J. Kennedy of the Rutgers Cancer Institute of New Jersey in New Brunswick told Reuters Health by phone that previous research has not shown bevacizumab to benefit patients with metastases and that this study was not adequately powered to show whether doctors can use this therapy now.

"Although this trial was small," added Dr. Kennedy, who also was not involved in the study, "it was important because the prognosis for our patients is not as great as we would like and recurrence rates are very high. I applaud the investigators for trying to improve the care we give our patients. This study definitely has some promising results and opens the door for further study."

The corresponding author did not respond to requests for comments.

The Beijing Municipal Commission of Science and Technology supported the study.

SOURCE: http://bit.ly/1TcWtJ2

Medicine 2015.