Ramucirumab for the treatment of gastric or gastro-esophageal junction cancer

ABSTRACT

Introduction: Gastric cancer remains one of the most lethal malignancy, accounting for an estimated 783,000 deaths worldwide in 2018. Although there are several approved drugs for the treatment of gastric cancer, the survival of patients with advanced disease remains dismal. Ramucirumab, a vascular endothelial growth factor receptor-2 inhibitor, is an important new targeted drug approved for gastric and gastroesophageal adenocarcinoma (GEJ) in second-line setting.

Areas covered: In this article, we have reviewed the role of ramucirumab in the management of gastric and GEJ adenocarcinoma. A comprehensive review of various clinical trials is presented that support the use of ramucirumab in gastric cancer.

Expert opinion: In our opinion, ramucirumab should be considered as a standard of care option, either alone or with paclitaxel, after progression on first-line therapy for advanced or metastatic disease. The results of large, randomized phase III clinical trials show benefit of ramucirumab on median overall survival (OS). However, the benefit is limited, with only about two months OS benefit of using ramucirumab with paclitaxel compared to paclitaxel alone. Novel combination therapies, such as ramucirumab with other targeted agents and immune checkpoint inhibitors in ongoing clinical trials, may provide important information to further improve the patient outcomes.

KEYWORDS:

• Ramucirumab
• gastric cancer
• gastroesophageal adenocarcinoma
• VEGFR-2 inhibitors
• targeted therapy

Article Highlights

• Ramucirumab is a fully humanized monoclonal antibody that inhibits vascular endothelial growth factor receptor-2.

• Ramucirumab has been approved by FDA to be used in second-line treatment either as a single agent or in combination with paclitaxel in gastric or GEJ adenocarcinoma.

• Ramucirumab should be considered as a standard of care option after progression on first-line therapy for advanced or metastatic disease. The results of pivotal phase III clinical trials, REGARD and RAINBOW, show clear efficacy benefit of ramucirumab.

• Ramucirumab is generally well tolerated. However, clinicians should be aware of certain severe adverse events including thromboembolic events, hypertension, hemorrhage and gastrointestinal perforation.

• There are numerous ongoing trials that are evaluating the role of combination of ramucirumab with novel agents both in metastatic and in perioperative setting. Specifically, the combination of ramucirumab and immune checkpoint inhibitors is currently being pursued in several ongoing clinical trials.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.