Ramucirumab

(Cyramza®)

Ramucirumab

Drug updated on 11/1/2024

Dosage FormInjection (intravenous; 100 mg/10 mL [10 mg/mL], 500 mg/50 mL [10 mg/mL])
Drug ClassHuman vascular endothelial growth factor receptor 2 (VEGFR2) antagonists
Ongoing and
Completed Studies
ClinicalTrials.gov

Indication

  • Indicated as a single agent or in combination with paclitaxel, for treatment of advanced or metastatic gastric or gastro-esophageal junction adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy
  • Indicated in combination with erlotinib, for first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations
  • Indicated in combination with docetaxel, for treatment of metastatic non-small cell lung cancer with disease progression on or after platinum-based chemotherapy
  • Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving CYRAMZA
  • Indicated 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
  • Indicated as a single agent, for the treatment of hepatocellular carcinoma in patients who have an alpha fetoprotein of 400 ng/mL and have been treated with sorafenib

Latest News

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Summary
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  • This summary is based on the review of 29 systematic review(s)/meta-analysis(es). [1-29]
  • Gastroesophageal Adenocarcinoma (GEA): Ramucirumab (RAM) combined with FOLFIRI or irinotecan achieved an overall response rate (ORR) ranging from 22% to 38%, with a pooled ORR of 25.4%. In combination with paclitaxel, RAM improved median overall survival (mOS) to 9.3-12.2 months and median progression-free survival (mPFS) to 4.1-5.1 months compared to paclitaxel alone (mOS: 5.2-9.7 months, mPFS: 3.0-4.1 months).
  • Hepatocellular Carcinoma (HCC): RAM provided progression-free survival benefits (HR = 0.44) similar to regorafenib and cabozantinib, with an overall survival benefit (HR (hazard ratio) = 0.82) over placebo. However, regorafenib and cabozantinib offered greater overall survival (OS) improvements (HR = 0.62 and HR = 0.74, respectively).
  • Non-Small Cell Lung Cancer (NSCLC): RAM plus docetaxel achieved a median OS of 11.2 months in patients pretreated with immune checkpoint inhibitors (ICI) and 13.5 months in ICI-naive patients. Median PFS was 5.7 months for ICI-pretreated and 3.8 months for ICI-naive patients.
  • EGFR-Mutated NSCLC: RAM combined with erlotinib demonstrated progression-free survival outcomes comparable to osimertinib and dacomitinib, with no significant difference in overall survival among treatments.
  • Gastroesophageal Adenocarcinoma (GEA) Safety: For RAM combined with FOLFIRI or irinotecan, neutropenia and diarrhea were the most commonly reported adverse events. In combination with paclitaxel, hematological toxicities were frequent, with low discontinuation rates due to adverse events (3.3-6.3%).
  • Hepatocellular Carcinoma (HCC) Safety: Ramucirumab exhibited an established safety profile with no significant new safety concerns, showing consistent safety across patient subgroups.
  • EGFR-Mutated NSCLC Safety: RAM combined with erlotinib increased the incidence of serious adverse events, particularly diarrhea, proteinuria, and hypertension, showing a higher risk of serious adverse events compared to erlotinib alone.
  • Ramucirumab (RAM) demonstrated higher overall response rates (ORR) in gastroesophageal adenocarcinoma (GEA) patients pretreated with taxanes and improved progression-free survival (mPFS) in patients with prior anti-PD-1 exposure. In hepatocellular carcinoma (HCC), RAM showed effectiveness regardless of elevated AFP levels, and in non-small cell lung cancer (NSCLC), RAM combined with docetaxel had consistent effectiveness and safety across patients, regardless of prior ICI treatment. In EGFR-mutated NSCLC, RAM with erlotinib provided comparable PFS benefits across subgroups, including those with exon 19 deletions and L858R mutations.

Product Monograph / Prescribing Information

Document TitleYearSource
Cyramza (ramucirumab) Prescribing Information.2022Eli Lilly and Company

Systematic Reviews / Meta-Analyses

Document TitleYearSource
Ramucirumab plus FOLFIRI or irinotecan as second-line treatment for patients with gastroesophageal adenocarcinoma: a review and meta-analysis of an emerging option2024Frontiers in Oncology
Efficacy and safety of second-line therapies for advanced hepatocellular carcinoma: a network meta-analysis of randomized controlled trials2024BMC Cancer
Real-World Effectiveness and Safety of Ramucirumab as a Second-Line Treatment for Patients with Unresectable Advanced or Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma in Japan and South Korea: A Systematic Literature Review2024Advances in Therapy
Comparative efficacy and safety of systemic therapy for advanced hepatocellular carcinoma: a systematic review and network meta-analysis2023Frontiers in Oncology
Clinical outcomes of ramucirumab plus docetaxel in the treatment of patients with non-small cell lung cancer after immunotherapy: a systematic literature review2023Frontiers in Oncology
Comparison of the efficacy and safety of first-line treatments for of advanced EGFR mutation-positive non-small-cell lung cancer in Asian populations: a systematic review and network meta-analysis2023Frontiers in Pharmacology
Front-line therapy for brain metastases and non-brain metastases in advanced epidermal growth factor receptor-mutated non-small cell lung cancer: a network meta-analysis2023Chinese Medical Journal
Safety of Anti-Angiogenic Drugs in Pediatric Patients with Solid Tumors: A Systematic Review and Meta-Analysis2022Cancers
Efficacy and Safety of Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitor Combination Therapy as First-Line Treatment for Patients with Advanced EGFR-Mutated, Non-Small Cell Lung Cancer: A Systematic Review and Bayesian Network Meta-Analysis2022Cancers
Overall Survival Benefits of First-Line Treatments for Asian Patients with Advanced Epidermal Growth Factor Receptor-Mutated NSCLC Harboring Exon 19 Deletion: A Systematic Review and Network Meta-Analysis2022Cancers
Impact of Smoking Status in Combination Treatment with EGFR Tyrosine Kinase Inhibitors and Anti-Angiogenic Agents in Advanced Non-Small Cell Lung Cancer Harboring Susceptible EGFR Mutations: Systematic Review and Meta-Analysis2022Journal of Clinical Medicine
Overall Survival Benefits of First-Line Treatments for Asian Patients With Advanced EGFR-Mutated NSCLC Harboring L858R Mutation: A Systematic Review and Network Meta-Analysis2022JTO Clinical and Research Reports
Prognostic and Predictive Factors in Patients with Advanced HCC and Elevated Alpha-Fetoprotein Treated with Ramucirumab in Two Randomized Phase III Trials2022Clinical Cancer Research
Efficacy and safety of first-line therapies in EGFR-mutated advanced non-small-cell lung cancer: a network meta-analysis2022Future Oncology
Second-line treatments for Advanced Hepatocellular Carcinoma: A Systematic Review and Bayesian Network Meta-analysis2022Clinical and Experimental Medicine
Comparative efficacy and safety for second-line treatment with ramucirumab, regorafenib, and cabozantinib in patients with advanced hepatocellular carcinoma progressed on sorafenib treatment: A network meta-analysis2021Medicine
Toward a Treatment Sequencing Strategy: A Systematic Review of Treatment Regimens in Advanced Gastric Cancer/Gastroesophageal Junction Adenocarcinoma2021The Oncologist
Ramucirumab in patients with previously treated advanced hepatocellular carcinoma: Impact of liver disease aetiology2021Liver International
Evidence-Based Management of Hepatocellular Carcinoma: Systematic Review and Meta-analysis of Randomized Controlled Trials (2002-2020)2021Gastroenterology
Comparative efficacy of treatments for previously treated patients with advanced esophageal and esophagogastric junction cancer: A network meta-analysis2021PloS One
Early Weight Loss as a Prognostic Factor in Patients with Advanced Gastric Cancer: Analyses from REGARD, RAINBOW, and RAINFALL Phase III Studies2021The Oncologist
Efficacy and safety of anti-angiogenic drugs combined with erlotinib in the treatment of advanced non-small cell lung cancer: a meta-analysis of randomized clinical trials2021Annals of Palliative Medicine
The integration of immune checkpoint inhibitors with VEGF targeted agents in advanced gastric and gastroesophageal adenocarcinoma: a review on the rationale and results of early phase trials2021Journal of Hematology & Oncology
Role of Antiangiogenic Agents Combined With EGFR Tyrosine Kinase Inhibitors in Treatment-naive Lung Cancer: A Meta-Analysis2021Clinical Lung Cancer
Optimizing Survival and the Changing Landscape of Targeted Therapy for Intermediate and Advanced Hepatocellular Carcinoma: A Systematic Review2021Journal of the National Cancer Institute
Comparative Efficacy and Safety of Anti-PD-1/PD-L1 Immune Checkpoint Inhibitors for Refractory or Relapsed Advanced Non-Small-Cell Lung Cancer-A Systematic Review and Network Meta-Analysis2020Cancers
Efficacy and Safety of Epidermal Growth Factor Receptor (EGFR) Inhibitors Plus Antiangiogenic Agents as First-Line Treatments for Patients With Advanced EGFR-Mutated Non-small Cell Lung Cancer: A Meta-Analysis2020Frontiers in Oncology
Role of Systemic Treatment for Advanced/Metastatic Gastric Carcinoma in the Third-Line Setting: A Bayesian Network Analysis2020Frontiers in Oncology
Second-line treatment strategy for urothelial cancer patients who progress or are unfit for cisplatin therapy: a network meta-analysis2019BMC Urology

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