Cyramza

Ramucirumab Instructions
Generic name: Ramucirumab
Trade name: Cyramza
Full names: Ramucirumab, Ramucirumab, Cyramza

Indications:
(1) As a single agent or in combination with paclitaxel (paclitaxel), used for advanced disease progression during or after fluorouracil-containing or platinum-containing chemotherapy. or patients with metastatic gastric or gastroesophageal junction adenocarcinoma (GEJA); (2) combined with docetaxel for patients with metastatic non-small cell lung cancer (NSCLC) whose disease has worsened during or after platinum-containing chemotherapy; (3) combined with FOLFIRI The regimen is used for patients with metastatic colorectal cancer (mCRC) whose disease has progressed during or after receiving bevacizumab, oxaliplatin, and fluorouracil; (4) as a monotherapy for the treatment of alpha-fetoprotein (AFP) ≥400ng/ mL of hepatocellular carcinoma (HCC).

Usage and dosage:
Non-small cell lung cancer
In combination with docetaxel for metastatic non-small cell lung cancer (NSCLC) and disease progression during or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor mutations should undergo genetic testing to detect whether EGFR or ALK gene mutations have occurred before receiving ramucirumab treatment.
Infuse 10 mg/m² approximately 1 hour before intravenous infusion of docetaxel (75 mg/m²) kg intravenously, as an intravenous infusion on day 1 of a 21-day cycle
Continue until disease progression or unacceptable toxicity

Gastric Cancer
As a single agent or in combination with paclitaxel, for the treatment of advanced gastric cancer or gastroesophageal junction adenocarcinoma before or after disease progression on prior fluoropyrimidine or platinum-containing chemotherapy
Single dose or in combination with paclitaxel: 8 mg/kg intravenously every two weeks; Infuse over 1 hour
Paclitaxel dose (if given in combination): 80 mg/m once weekly, every 28 days for 3 weeks
When given in combination, give ramucirumab before giving paclitaxel (Ramucirumab)
Continue until disease progression or unacceptable toxicity

Colorectal Cancer
Investigated in combination with FOLFIRI for the treatment of patients with metastatic colorectal cancer (mCRC) whose disease has progressed on a first-line bevacizumab, oxaliplatin, and fluoropyrimidine-containing regimen
8 mg/kg intravenously every two weeks; Administer by intravenous infusion 60 minutes before FOLFIRI administration
Continue until disease progression or unacceptable toxicity

Hepatocellular Carcinoma
Sorafenib has been studied as monotherapy for hepatocellular carcinoma (HCC) with alpha-fetoprotein (AFP) ≥400 ng/mL
8 mg/IV every 2 weeks kg
Continue until disease progression or unacceptable toxicity

Adverse reactions:
> 10%
All grades unless otherwise stated
Gastrointestinal cancer (plus paclitaxel)
Fatigue/asthenia (57%)
Neutropenia (54%)
Diarrhea (32%)
Estistaxis (31%)
Peripheral edema (25%)
Stomatitis (20%) )
Proteinuria (17%)
Hypertension (25%)
Infusion-related reactions (16%)
Hypertension grade 3-4 (15%)
Thrombocytopenia (13%)
Hypoalbuminemia (11%)
NSCLC (plus docetaxel)
Neutral Granulocytopenia (55%)
Fatigue/weakness (55%)
Stomatitis/mucosal inflammation (37%)
Estistaxis (19%)
Febrile neutropenia (16%)
Peripheral edema (16%)
Thrombocytopenia (13%)
Increased tear production Plus (13%)
Hypertension (11%)

HCC
Thrombocytopenia (46%)
Fatigue (36%)
Hypoalbuminemia (33%)
Hyponatremia (32%)
Peripheral edema, hypertension, abdominal pain (25%)
Neutropenia (24%)
Decreased appetite (23%)
Proteinuria (20%)
Nausea (19%)
Ascites (18%)
Hypocalcemia (16%)
br>Headache (14%)
Epistaxis (14%)
Insomnia (11%)

1-10%
Gastrointestinal bleeding events, gastric cancer (10%)

<1%
Gastrointestinal perforation (single dose) (0.7%)
Reversible posterior leukoencephalopathy syndrome (<0.1%)

Post-Marketing Reports
Thrombotic microangiopathy

Contraindications:
None

Precautions:
Increased risk of bleeding and gastrointestinal hemorrhage, including serious and sometimes fatal bleeding events; Permanent discontinuation in patients who experience severe bleeding
Serious, sometimes fatal arterial thromboembolic events, including myocardial infarction, cardiac arrest, cerebrovascular accidents, and cerebral ischemia, reported in clinical trials
An increased incidence of severe hypertension has been reported; Control hypertension before starting treatment and monitor blood pressure q2 weeks or more frequently as directed; Temporarily discontinue treatment for severe hypertension
Infusion-related reactions observed include severe/tremor, back pain/cramps, chest pain and/or tightness, chills, flushing, dyspnea, wheezing, hypoxia, and paresthesia; in severe cases, symptoms include bronchospasm, supraventricular tachycardia, and hypotension
Ramucirumab is an anti-angiogenic therapy that may increase the risk of gastrointestinal perforation and affect wound healing; withhold before surgery; Permanently discontinue ramucirumab in patients who experience gastrointestinal perforation.
Impaired wound healing can occur with antibodies used to inhibit the VEGF pathway; withhold for 28 days before elective surgery; administer for at least 28 days after major surgical procedures until complete healing; discontinue if patient develops wound healing complications requiring medical intervention
Clinical worsening, manifested by new or worsening encephalopathy, ascites, or hepatorenal syndrome, reported in patients with Child-Pugh B or C cirrhosis; Use only when benefits outweigh risks
Reversible posterior leukoencephalopathy syndrome (RPLS) has been reported (rare); discontinuation of ramucirumab
Severe proteinuria, including nephrotic syndrome, has been reported, especially when taken with FOLFIRI
Hypothyroidism may occur; Monitor thyroid function during treatment
Based on its mechanism of action, ramucirumab can cause fetal harm when administered to pregnant women

Storage:
Unopened vials
Refrigerate at 2-8°C ( 36-46°F)
Place vial in outer carton to protect from light

Dilute infusion
Administer within 24 hours of dilution
Refrigerate at 2-8°C (36-46°F) or refrigerate at room temperature (i.e. below 25°C) for 4 hours [77°F])
Do not freeze
Discard partially used vials

Mechanism of action:
Ramucirumab is a human vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor that specifically binds to VEGF receptor 2 and blocks the coordination of VEGF ligands, VEGF-A, VEGF-C and VEGF-D. Thus, ramucirumab can inhibit ligand-induced activation of VEGF receptor 2, thereby inhibiting ligand-induced proliferation and migration of human endothelial cells.

Efficacy and safety:
Dr. Richard Pazdur, director of the Office of Hematology and Oncology Drugs in the FDA's Center for Drug Evaluation and Research, pointed out in a statement that ramucirumab has been proven to prolong patients' lives and slow down tumor growth, making it a new treatment option. The approval was based on a study of 355 patients with unresectable or metastatic gastric or gastroesophageal junction cancer. The median overall survival of patients in the ramucirumab group was 5.2 months compared with 3.8 months in the placebo group, with a hazard ratio (HR) of 0.78 (P=0.047). The progression-free survival of the Ramucirumab treatment group was also better than that of the placebo group, which was 2.1 months and 1.3 months respectively, with statistical significance (HR, 0.48). In another study comparing ramucirumab combined with paclitaxel and paclitaxel monotherapy, patients in the combination group also had an advantage in overall survival.
Cyramza has received FDA approval as a second-line therapy for the treatment of gastric cancer, NSCLC, colorectal cancer, and hepatocellular carcinoma (HCC).
449 patients with metastatic NSCLC carrying EGFR gene mutations (exon 19 deletion or exon 21 L858R substitution mutation) participated in the phase 3 RELAY trial. They were randomly assigned to receive a combination of Cyramza and erlotinib, or placebo and erlotinib. Compared with the PFS of 12.4 months in the erlotinib group, the PFS in the combination therapy group was 19.4 months, reaching the primary endpoint of significantly extending PFS. Improvements in secondary or exploratory endpoints such as duration of response, time to second progression or death (PFS2), and time on targeted therapy were seen in the combination therapy group.