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Ramucirumab: successfully targeting angiogenesis in gastric cancer
Milind Javle1, Elizabeth C Smyth2, Ian Chau2
1Department of Gastrointestinal Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas. mjavle@mdanderson.org.
Abstract:
Gastric cancer is the fourth most common cancer globally and represents the second most common cause of cancer-related mortality. Early detection, aggressive surgical resection, and postoperative adjuvant therapy have led to survival improvement for early-stage gastric cancer, particularly in Asian countries. Unfortunately, advanced gastric cancer continues to pose a formidable challenge with few gains being reported recently. Trastuzumab was the first targeted agent to be approved for the treatment of advanced gastric cancer in 2010. The failure of the AVAGAST trial was a setback for antiangiogenic therapy for this disease. Ramucirumab is a monoclonal antibody that binds to VEGF-R2 and prevents its activation. The recent REGARD trial was a randomized phase III trial of ramucirumab vs. placebo for patients with advanced, pretreated gastric cancer that met its primary endpoint of increased overall survival. The toxicity of ramucirumab was modest in this setting, with an increased risk of grade 3 or higher hypertension (8% vs. 3%, with ramucirumab and placebo, respectively). The subsequent RAINBOW trial of paclitaxel plus ramucirumab vs. paclitaxel plus placebo for advanced pretreated gastric cancer confirmed the survival advantage of this antiangiogenic agent in gastric cancer. Ramucirumab is the first FDA-approved therapy for advanced gastric cancer after prior chemotherapy.
Insights
Ramucirumab, a VEGF-R2 inhibitor, offers improved survival for advanced gastric cancer patients. This therapy, tested in the REGARD and RAINBOW trials, shows modest toxicity and is the first FDA-approved option after chemotherapy.
Area of Science:
- Oncology
- Gastroenterology
- Pharmacology
Background:
- Gastric cancer is a leading cause of cancer mortality worldwide.
- Advanced gastric cancer remains challenging to treat, with limited recent therapeutic advancements.
- Trastuzumab was the first targeted therapy approved in 2010, but antiangiogenic therapy faced setbacks.
Purpose of the Study:
- To evaluate the efficacy and safety of ramucirumab in patients with advanced gastric cancer.
- To assess ramucirumab as a monotherapy and in combination with paclitaxel for pretreated advanced gastric cancer.
Main Methods:
- The REGARD trial: a randomized phase III trial comparing ramucirumab to placebo in pretreated advanced gastric cancer patients.
- The RAINBOW trial: a randomized phase III trial comparing paclitaxel plus ramucirumab to paclitaxel plus placebo in pretreated advanced gastric cancer patients.
Main Results:
- Ramucirumab monotherapy (REGARD trial) significantly increased overall survival compared to placebo.
- Ramucirumab plus paclitaxel (RAINBOW trial) demonstrated a survival advantage over paclitaxel plus placebo.
- Ramucirumab exhibited modest toxicity, with a notable increase in hypertension.
Conclusions:
- Ramucirumab is the first FDA-approved therapy for advanced gastric cancer following prior chemotherapy.
- Ramucirumab represents a significant advancement in the treatment of advanced gastric cancer, particularly in combination therapy.
- Targeted antiangiogenic therapy with ramucirumab shows promise for improving outcomes in advanced gastric cancer.
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