Ramucirumab (Cyramza) — Clinical FAQs

Question 1

What is Ramucirumab FDA-approved to treat?

Accepted Answer

Ramucirumab is FDA-approved for the following oncology indications: 1. Advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma after prior fluoropyrimidine- or platinum-containing chemotherapy — approved April 2014 as monotherapy (REGARD trial) 2. Advanced gastric or GEJ adenocarcinoma in combination with paclitaxel after prior fluoropyrimidine- or platinum-containing chemotherapy — approved November 2014 (RAINBOW trial) 3. Metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy, in combination with docetaxel — approved December 2014 (REVEL trial) 4. Metastatic colorectal cancer (mCRC) with disease progression on or after bevacizumab, oxaliplatin, and fluoropyrimidine-based chemotherapy, in combination with FOLFIRI — approved April 2015 (RAISE trial) 5. Hepatocellular carcinoma (HCC) after sorafenib in patients with AFP ≥400 ng/mL — approved May 2019 (REACH-2 trial).

Question 2

How does Ramucirumab work (mechanism of action)?

Accepted Answer

Ramucirumab is a fully human IgG1 monoclonal antibody that specifically binds the extracellular domain of vascular endothelial growth factor receptor-2 (VEGFR-2) with high affinity, blocking binding of all VEGFR-2 ligands — VEGF-A, VEGF-C, and VEGF-D. By occupying the VEGF-binding domain of VEGFR-2, ramucirumab prevents receptor dimerization, autophosphorylation, and downstream activation of pro-angiogenic signaling cascades including the PI3K/AKT, MAPK/ERK, and PLC-γ pathways. The resultant inhibition of tumor neovascularization deprives tumors of oxygen and nutrients required for proliferation and metastasis. Unlike small molecule VEGFR inhibitors, ramucirumab's antibody format provides high target specificity with minimal off-target kinase inhibition.

Question 3

How is Ramucirumab administered?

Accepted Answer

Ramucirumab is administered Intravenous (IV). Gastric/GEJ cancer (monotherapy or with paclitaxel): 8 mg/kg IV every 2 weeks.

Question 4

What are the most common side effects of Ramucirumab?

Accepted Answer

The most commonly reported side effects of Ramucirumab (≥10% incidence) include: Hypertension (16-26%), Proteinuria (17-19%), Headache (9-15%), Diarrhea (14%), Fatigue (35-57%; when combined with chemotherapy) and others (12 total). Consult your oncologist for complete prescribing information.

Question 5

Does Ramucirumab have a black box warning?

Accepted Answer

Yes. Ramucirumab carries FDA black box warning(s) regarding: 1. Hemorrhage: Severe and sometimes fatal hemorrhagic events including GI hemorrhage have occurred. Permanently discontinue for severe hemorrhage. 2. Gastrointestinal Perforation: Potentially fatal GI perforation occurred in clinical trials. Permanently discontinue for GI perforation. 3. Impaired Wound Healing: Withhold ramucirumab for at least 28 days prior to elective surgery. Resume no sooner than 28 days after surgery and complete wound healing. Withhold for wound healing complications.

Question 6

Is Ramucirumab safe during pregnancy?

Accepted Answer

Ramucirumab pregnancy safety: Contraindicated in pregnancy. Ramucirumab is expected to cause fetal harm based on its anti-angiogenic mechanism of action. Women of reproductive potential should use effective contraception during therapy and for 3 months after last dose. Breastfeeding is not recommended during therapy and for 3 months after last dose.. Oncologists should review the complete prescribing information and discuss reproductive risks with patients before initiating therapy.

Ramucirumab — Drug Monograph

Mechanism of Action

FDA Indications

Common Side Effects

Clinical Pearl

Related Therapies & Mechanisms