Ramucirumab

• Class: Monoclonal antibody – VEGFR-2 antagonist.
• Type: Fully human IgG1 mAb.

Mechanism of Action (MOA)

• Binds to VEGFR-2 → blocks binding of VEGF ligands (VEGF-A, VEGF-C, VEGF-D).

• Inhibits angiogenesis, reducing tumor blood supply → tumor growth suppression.
• Does not bind VEGFR-1 → more selective angiogenesis inhibition.

Clinical Uses

• Gastric or gastroesophageal junction adenocarcinoma – advanced or metastatic, typically second-line therapy (with paclitaxel).
• Metastatic non-small cell lung cancer (NSCLC) – second-line in combination with docetaxel.
• Hepatocellular carcinoma (HCC) – second-line after sorafenib.
• Investigational/less common: colorectal cancer, breast cancer (trials ongoing).

Dosing (Adults)

• Gastric/GEJ cancer: 8 mg/kg IV every 2 weeks (with paclitaxel).
• NSCLC: 10 mg/kg IV every 3 weeks (with docetaxel).
• Infuse over 60 minutes for first infusion, may shorten for subsequent doses if tolerated.
• No routine premedication required.

Toxicities

• Hypertension – common; monitor BP regularly.
• Proteinuria – monitor urinalysis/urine protein.
• Bleeding/hemorrhage – epistaxis, GI bleeding.
• GI perforation – rare but serious.
• Impaired wound healing – avoid surgery 28 days after or before therapy.
• Fatigue, diarrhea, neutropenia (from combination chemotherapy).

Monitoring

• Blood pressure (baseline and before each dose).
• Urinalysis / urine protein (baseline and periodically).
• CBC and renal function when used with chemotherapy.
• Signs of bleeding or thromboembolic events.
• Electrolytes and hepatic function as clinically indicated.

Summary

Ramucirumab (Cyramza®) is a VEGFR-2-targeted antiangiogenic monoclonal antibody used mainly in second-line gastric, NSCLC, and HCC. Key concerns are hypertension, proteinuria, bleeding, and impaired wound healing. Monitor BP, urine protein, and combination chemotherapy toxicities.