Gastric cancer is one of the most common cancers and a leading cause of cancer-related death worldwide. Surgical resection of the tumour is potentially curative at early stages; however, many patients still relapse following resection. Most patients with gastric cancer are diagnosed at an advanced stage or develop recurrence after surgery, and thus, combined therapies are the standard of care for stage 1B or higher gastric cancer.
Recently published guidelines of the National Comprehensive Cancer Network, European Society for Medical Oncology, and Pan-Asian European Society for Medical Oncology recommend Fluoropyrimidine- and platinum-based combination regimens, in combination with Trastuzumab as the first-line treatment for patients having unresectable locally advanced or metastatic gastric cancer who have human epidermal growth factor 2 (HER2)-positive tumours.
These guidelines also highlighted that Ramucirumab plus Paclitaxel is the preferred second-line treatment choice for patients with metastatic gastric cancer who failed first-line treatment with platinum- and Fluoropyrimidine-based combinations or Trastuzumab in combination with Cisplatin and 5-Fluorouracil/Cisplatin and Capecitabine.
Ramucirumab is a VEGFR-2-specific (vascular endothelial growth factor receptor-2) human IgG1 monoclonal antibody. The U.S. Food and Drug Administration (FDA) approved Ramucirumab as monotherapy or in combination with Paclitaxel for the treatment of patients with advanced or metastatic gastric or GEJ adenocarcinoma with disease progression on or after previous treatment with Fluoropyrimidine- or platinum-containing chemotherapy.
As per a paper published in Lancet, Ramucirumab is the first biological treatment given as a single drug that has survival benefits in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma progressing after first-line chemotherapy. In patients with gastric cancer, Ramucirumab should be administered at a dose of 8 mg/kg every 2 weeks as monotherapy or in combination with weekly Paclitaxel.
The common adverse reactions observed in single-agent Ramucirumab-treated gastric cancer patients are hypertension and diarrhoea. The side effects observed in patients treated with Ramucirumab with Paclitaxel are fatigue/asthenia, neutropenia, diarrhoea, and epistaxis. Ramucirumab is speculated to increase the risk of haemorrhage, including severe and rarely fatal haemorrhagic events; hence, Ramucirumab should be discontinued in patients who experience severe bleeding.
Therefore, blood pressure should be controlled prior to the initiation of Ramucirumab, monitored every 2 weeks, and continued to be well controlled throughout treatment. Patients should be educated on the signs and symptoms of venous thromboembolism, bleeding, home blood pressure monitoring, infusion-related reactions, and bowel perforation.
Finally, as the first monoclonal antibody to bind to the extracellular domain of the VEGFR-2, Ramucirumab has demonstrated an improvement in overall survival as monotherapy and in combination with paclitaxel in pre-treated patients with advanced gastric cancer. With its manageable toxicity profile, Ramucirumab provides practitioners with a safe and effective FDA-approved second-line therapy option for gastric cancer.
(Author is Member, American Society of Clinical Oncology (ASCO). Specialization in Cancer Biology from Johns Hopkins University (USA). Feedback: [email protected])
