Novel Agents Produce Encouraging Trends in Gastric Cancer


Key Points

  • New directions in research may lead to improved options for gastric cancer.
  • Drugs under study include those targeting HER2, C-MET, VEGF, and VEGFR-2.

Several novel agents targeting the HER2, C-MET, and VEGF receptors have achieved encouraging results in gastric cancer, which is the second leading cause of cancer death worldwide. Charles Fuchs, MD, of Dana-Farber Cancer Institute, Boston, reviewed these new approaches in a presentation at the Chemotherapy Foundation Symposium XXXI.

“It is an exciting time in gastric cancer. Hopefully, with these new treatments we will move the needle forward on survival," said Dr. Fuchs.

Targeting the HER2, C-MET, and VEGF Receptors

Trastuzumab (Herceptin) is approved for front-line therapy of HER2-positive gastric cancer, and ado-trastuzumab emtansine (Kadcyla, previously known as T-DM1) is now under study in HER2-positive gastric cancer. A phase III study is comparing ado-trastuzumab emtansine every 3 weeks vs ado-trastuzumab emtansine weekly vs placebo in HER2-positive advanced gastric cancer.

More recently, C-MET inhibition has become an area of interest. In the overall analysis of a recent phase II study, the C-MET inhibitor rilotumumab in combination with epirubicin, cisplatin, and capecitabine showed a trend toward improved survival. An exploratory analysis found that the survival benefit was restricted to patients whose tumors had high MET expression, whereas the addition of rilotumumab to chemotherapy was unfavorable in those with low MET expression.

In addition, the ongoing RILOMET-1 study is evaluating rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line therapy in 450 patients with MET-positive gastric or gastroesophageal junction cancer.

Anti-VEGF therapy with bevacizumab (Avastin) appeared to improve survival in more than 700 patients with gastric cancer in the AVAGAST trial. However, there were regional differences; bevacizumab had the best outcomes in patients enrolled in the Americas and Western Europe, while much less benefit was observed in patients from Asian countries.

Promising Results With Ramucirumab

Ramucirumab is a monoclonal antibody against VEGFR2 that was recently designated by the FDA for priority review as a single-agent treatment for gastric cancer. In the REGARD study, 355 patients with gastric and gastroesophageal junction adenocarcinoma were randomly assigned to ramucirumab vs placebo. The monoclonal antibody significantly improved overall survival (5.2 months vs 3.8 months for placebo) and progression-free survival (median of 2.1 months vs 1.3 months for placebo). The 12-week progression-free survival rate was 40% vs 16% for placebo.

Toxicities were comparable between ramucirumab and placebo groups; adverse events of any grade were reported by 57% of the ramucirumab group and 58% of the placebo group. Although more hypertension was seen in the ramucirumab-treated group, there were no new safety signals in the trial.

Ramucirumab also showed promising results in the RAINBOW study, which included 663 patients with gastric cancer for whom first-line therapy failed and who were randomly assigned to paclitaxel plus ramucirumab vs paclitaxel plus placebo. A recent news release reported significant improvement in progression-free and overall survival in those treated with ramucirumab, but full details of the study are not yet available.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.