Summary

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• Cyramza (ramucirumab) is indicated as a single agent or in combination with paclitaxel for the treatment of advanced or metastatic gastric or gastro-esophageal junction adenocarcinoma with disease progression on or after prior fluoropyrimidine- or platinum-containing chemotherapy. It is also used in combination with erlotinib for the first-line treatment of metastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations. Additionally, Cyramza is combined with docetaxel for the 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 must have experienced disease progression on FDA-approved therapy for these aberrations before receiving Cyramza. Furthermore, it is used 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. As a single agent, Cyramza is indicated for the treatment of hepatocellular carcinoma in patients who have an alpha-fetoprotein of ≥400 ng/mL and have been treated with sorafenib.
• This summary is based on the review of 15 systematic review(s)/meta-analysis(es). ^[1-15]
• Non-Small Cell Lung Cancer (NSCLC): Ramucirumab combined with docetaxel improved overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) in metastatic NSCLC patients after platinum-based chemotherapy. In patients pre-treated with immune checkpoint inhibitors (ICIs), the median PFS was 5.7 months and OS was 11.2 months, while in ICI-naïve patients, the median PFS was 3.8 months and OS was 13.5 months.
• Esophageal and Esophagogastric Junction (EGJ) Cancer: Ramucirumab plus chemotherapy significantly improved OS compared to chemotherapy alone in advanced esophageal/EGJ cancer, particularly in adenocarcinoma (AC) and squamous cell carcinoma (SCC) subtypes.
• Hepatocellular Carcinoma (HCC): Ramucirumab showed an OS benefit across various liver disease etiologies in patients with baseline AFP ≥ 400 ng/mL. In second-line settings, ramucirumab demonstrated improved OS compared to placebo, especially in patients with elevated AFP.
• Gastric Cancer: Ramucirumab with paclitaxel was recommended as the preferred second-line treatment, showing superior OS and PFS rankings in network meta-analyses, particularly in the second-line treatment comparisons.
• Ramucirumab + Docetaxel: Demonstrated a consistent safety profile with no new safety signals reported, but there was a higher incidence of grade 3-5 treatment-related adverse events (G3-5AEs) compared to nivolumab and atezolizumab.
• Erlotinib + Ramucirumab: Associated with increased toxicity compared to other combinations and standard chemotherapy, with particularly higher toxicity observed when combined with bevacizumab or pemetrexed-based chemotherapy.
• Ramucirumab + Chemotherapy (Esophageal/EGJ Cancer): Resulted in increased toxicity compared to chemotherapy alone, though toxicity remained within acceptable limits.
• Population Types and Subgroup Considerations: Ramucirumab-based treatments were effective in NSCLC patients regardless of prior ICI treatment status, in esophageal/EGJ cancer patients with either adenocarcinoma or squamous cell carcinoma, across different liver disease etiologies in hepatocellular carcinoma (HCC) patients, particularly with elevated AFP levels, and in gastric cancer patients in second-line treatment irrespective of peritoneal metastases. No new safety concerns emerged across these subgroups, with increased toxicity observed in some treatments but within acceptable limits.