Ramucirumab (Cyramza)

General information

Class/mechanism: Recombinant human IgG1 monoclonal antibody, VEGFR2 (vascular endothelial growth factor receptor 2) antagonist. Ramucirumab binds VEGFR2 and blocks VEGFR ligands, VEGF-A, VEGF-C, and VEGF-D, which inhibits angiogenesis.
Route: IV
Extravasation: no information

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is established (work in progress)

• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Non-small cell lung cancer

Diseases for which it is used

• Esophageal adenocarcinoma
• Urothelial carcinoma

Patient drug information

• Ramucirumab (Cyramza) patient drug information (Chemocare)
• Ramucirumab (Cyramza) package insert
• Ramucirumab (Cyramza) patient drug information (UpToDate)

History of changes in FDA indication

Colorectal cancer

• 2015-04-24: Approved in combination with FOLFIRI, for the treatment of metastatic colorectal cancer with disease progression on or after prior therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. (New disease entity; based on RAISE)

Gastric cancer

• 2014-04-21: Initial approval for the treatment of patients with advanced or metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after prior treatment with fluoropyrimidine- or platinum- containing chemotherapy. (Based on REGARD)
• 2014-11-05: Approval and indication expanded for use in combination with paclitaxel for the treatment of patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. (Requirement for prior lines of treatment removed; based on RAINBOW)

Hepatocellular carcinoma

• 2019-05-10: Approved as a single agent for hepatocellular carcinoma (HCC) in patients who have an alpha fetoprotein (AFP) of at least 400 ng/mL and have been previously treated with sorafenib. (New disease entity; based on REACH-2)

Non-small cell lung cancer

• 2014-12-12: Approved for use in combination with docetaxel for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with disease progression on or after platinum-based chemotherapy. (New disease entity; based on REVEL)
• 2020-05-29: Approved in combination with erlotinib for first-line treatment of metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations. (Approval expanded to first-line setting in EGFR+ NSCLC; based on RELAY)

History of changes in EMA indication

• 2014-12-16: Initial marketing authorization as Cyramza.

History of changes in Health Canada indication

• 2015-07-16: Initial notice of compliance as a single agent for the treatment of patients with advanced or metastatic gastric cancer or gastro-esophageal junction adenocarcinoma with disease progression on or after prior platinum and fluoropyrimidine chemotherapy.
• 2015-07-16: Initial notice of compliance in combination with paclitaxel for the treatment of patients with advanced or metastatic gastric cancer or gastro-esophageal junction adenocarcinoma with disease progression on or after prior platinum and fluoropyrimidine chemotherapy.

History of changes in PMDA indication

• 2015-03-26: Initial approval for the treatment of unresectable advanced or recurrent gastric cancer.
• 2016-05-23: New additional indication and a new dosage for the treatment of unresectable advanced or recurrent colorectal cancer.
• 2016-06-20: New additional indication and a new dosage for the treatment of unresectable advanced/relapsed non-small cell lung cancer.
• 2019-06-18: New indication for the treatment of patients with unresectable hepatocellular carcinoma whose serum AFP level is greater than 400 ng/mL and conditions have progressed after cancer chemotherapy.

Also known as

• Code names: IMC-1121B, LY-3009806
• Brand name: Cyramza