Opdivo

Nivolumab (Opdivo) instructions
Common name: Nivolumab
Trade name: Opdivo
All names: Nivolumab, Opdivo, Nivolumab, O drug, Opdivo, Nivolumab, Opdyta

Indications:
Metastatic melanoma, renal cancer, treated advanced non-small cell lung cancer, metastatic lung cancer.

Usage and dosage:
The recommended dose is 3mg/kg. Since its dosage forms are 40mg/4mL and 100mg/10mL, the patient's weight is usually more than 60kg, so the usual dosage is 200-240mg each time. The patient takes the medicine once every two weeks, and the time for each medication is no less than 30 minutes.

Adverse reactions:

> 10% (all grades)

Melanoma
Increased AST (28%)
Hyponatremia (25%)
Increased alkaline phosphatase (22%)
Rush (21%)
Pruritus (19%)
Cough (17%)
Increased ALT (16%)
Hyperkalemia (15%)
URTI (11%)

Non-small cell lung cancer
Fatigue (50%)
Lymphopenia (47%)
Dyspnea, hyponatremia (38%)
Musculoskeletal pain (36% )
Cough (32%)
Nausea (29%)
Increased creatinine (22%)
Hypercalcemia, hypokalemia, hypomagnesemia (20%)
vomiting, weakness (19%)
hypocalcemia, hyperkalemia, diarrhea (18%)
edema, fever (17%) )
Abdominal pain, rash, increased AST (16%)
Alkaline phosphatase, increased thrombocytopenia (14%)
Chest pain, arthralgia, decreased appetite and weight loss (13%)
Increased ALT (12%)

1-10% (all grades)Melanoma
Peripheral edema (10%)

Non-small cell lung cancer
Pneumonia (10%)
Pain (10%)

1-10% (grade 3-4)
Melanoma
Hyponatremia (5%)
AS Increased T (2.4%)
Increased alkaline phosphatase (2.4%)
Hyperkalemia (2%)
Increased ALT (1.6%)

Non-small cell lung cancer
Dyspnea (9%)
Fatigue (7%)
Musculoskeletal pain (6%)
1 -10% (Other clinically important adverse reactions)
Melanoma
Heart disease: Ventricular arrhythmias
Ocular disease: Iridocyclitis
General diseases and administration site conditions: Infusion-related reactions
Immune-mediated diseases: Severe pneumonia or interstitial lung disease, including fatal cases; Colitis; Hepatitis; Nephritis; Thyroid disease; Other immune diseases (pancreatitis, uveitis, demyelination, autoimmune neuropathies, adrenocortical insufficiency, facial and abducens nerve palsies, hypophysitis, polymyalgia rheumatica, diabetic ketoacidosis, hypopituitarism, Guillain– Barre syndrome, myasthenic syndrome)
Investigations: increased amylase, increased lipase
Nervous system disorders: dizziness, peripheral and sensory neuropathy
Skin and subcutaneous tissue disorders: exfoliative dermatitis, erythema multiforme, vitiligo, psoriasis

Non-small cell lung Cancer
General diseases and administration site conditions: Stomatitis
Nervous system disorders: Peripheral neuropathy
Infections and infections: Bronchitis, upper respiratory tract infections

Contraindications:
Patients with hypersensitivity to the active ingredient or to any of the excipients listed (Ingredients).

Note:
Immune-mediated pneumonitis may occur; moderate and permanent discontinuation for severe or life-threatening pneumonitis
Immune-mediated colitis has been reported; discontinue use and permanently discontinue use in patients with moderate or severe pneumonitis and permanently discontinue life-threatening colitis
Immune-mediated hepatitis was observed in clinical trials; monitor for changes in liver function; moderate and permanent discontinuation for severe or life-threatening elevations in transaminases or total bilirubin
Immune-mediated nephritis and renal dysfunction may occur; Monitor for changes in renal function; withhold treatment for moderate and permanent increases in serum creatinine for severe or life-threatening increases in serum creatinine; withhold treatment for moderate (Grade 2) or severe (Grade 3) serum creatinine; permanently discontinue treatment for life-threatening (Grade 4) increases in serum creatinine Immune-mediated encephalitis may occur; Withhold treatment and evaluate patients with new onset of moderate to severe neurological signs or symptoms to exclude infectious or other causes of moderate to severe neurological deterioration; evaluation may include, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture; if other causes are excluded, in patients with immune-mediated encephalitis, administer corticosteroids at a dose of 1-2 mg/kg/day prednisone equivalent, followed by a corticosteroid taper; Permanently discontinue treatment for immune-mediated encephalitis
Other clinically significant and potentially fatal immune-mediated adverse reactions may occur after discontinuation of treatment (e.g., myocarditis, rhabdomyolysis, myositis, uveitis, iritis, pancreatitis)
Serious infusion reactions have been reported (rare, <1%); discontinue if severe or life-threatening; Interrupting or slowing the infusion in patients with mild or moderate infusion reactions can cause fetal harm; potential risks to the fetus and the use of effective contraception are recommended (see Pregnancy and Lactation) Monitor for hyperacute graft-versus-host disease (GVHD), grade 3-4 acute GVHD, febrile syndrome requiring steroids, hepatic veno-occlusive disease, and other immune-mediated adverse reactions; Transplantation-related mortality has occurred
Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after treatment with PD-1 receptor blocking antibodies; Complications may occur despite intervening treatments between PD-1 blockade and allogeneic HSCT; Consider the benefits versus risks of treatment with PD-1 receptor blocking antibodies before or after allogeneic HSCT
If uveitis occurs with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome that has been observed in patients receiving the drug alone or in combination with ipilimumab, which may May require treatment with systemic steroids to reduce permanent vision loss

Storage:
Unopened vial
Refrigerate at 2-8°C (36-46°F)
Store in original packaging away from light
Do not freeze

Dilute mixture
Room temperature: store up to 8 hours from time of preparation; This includes room temperature storage of the mixture in the IV container and the time of administration of the infused OR
Refrigerate at 2-8°C (36-46°F) for no more than 24 hours from the time of preparation of the mixture
Do not freeze

Mechanism of action:
T cells are a type of immune cell that can specifically kill target cells that are harmful to the body. However, some malignant melanoma cells can transmit signals to the PD-1 receptor of T cells, causing T cells to be in a non-responsive state, thus losing the ability to attack malignant melanoma, leading to the growth of melanoma. OPDIVO specifically binds to the PD-1 receptor on T cells, preventing signals from malignant melanoma cells from reaching T cells, allowing T cells to function normally.

Efficacy and Safety:
Randomized, Phase 3 Study Compared with Docetaxel (CA209078)
The safety and efficacy of nivolumab 3 mg/kg as monotherapy in advanced or metastatic squamous and non-squamous NSCLC was evaluated in a phase 3, randomized, open-label study (CA209078). Patients with EGFR mutations in non-squamous NSCLC or patients with known ALK translocations were excluded. The study included patients (18 years or older) who had disease progression during or after prior platinum-containing two-drug chemotherapy and an ECOG performance status score of 0 or 1. Patients were eligible regardless of the PD-L1 expression status of their tumors before the study, and were stratified by PD-L1 expression (1% cutoff). Patients with previously treated brain metastases were eligible if their neurological condition had returned to baseline, corticosteroids were discontinued, or treatment was stable at <10 mg/day prednisone equivalent or at a reduced dose at least 2 weeks before enrollment.
A total of 504 patients were randomized in a 2:1 ratio to receive nivolumab 3 mg/kg (n = 338) intravenously over 60 minutes every 2 weeks or docetaxel (n = 166) 75 mg/m every 3 weeks. Treatment is continued as long as clinical benefit is observed or until the patient cannot tolerate treatment. Tumor assessments were performed every 6 weeks after randomization (per RECIST version 1.1). The primary efficacy outcome measure was overall survival (OS). Key secondary efficacy outcome measures were investigator-assessed ORR, PFS, and TTF (time to treatment failure). In addition, symptom improvement and overall health status were assessed using the Lung Cancer Symptom Score (LCSS) mean symptom burden index and the EQ-5D visual analogue scale (EQ-VAS), respectively.
Baseline characteristics were basically balanced between the two groups. The median age was 60.0 years (range: 39-85), with 25.2% ≥65 years and 2.4% ≥75 years. Most patients were Chinese (91.6%) and male (78.8%). 20.6% of all enrolled patients reported disease progression that was best response to their most recent prior regimen, and 53.6% received nivolumab or docetaxel within 3 months of completing their most recent prior regimen. Baseline ECOG performance status score was 0 (13.5%) or 1 (86.5%). 39.1% were squamous cell carcinoma, 70.2% were current smokers or former smokers, and 50.0% were PD-L1 expressors.
The study confirmed that patients randomized to nivolumab had a statistically significant improvement in overall survival compared with docetaxel when 301 events (79% of planned events in the final analysis) were observed at the prespecified interim analysis.
At the minimum follow-up of 8.8 months, the overall survival of the nivolumab group was better than that of the docetaxel group, with a hazard ratio (HR) of 0.68 [95% CI: 0.54, 0.87] and a stratified log-rank test p value of 0.0017. The median OS of the nivolumab group and docetaxel group were 11.99 months (95% CI: 10.35-14.00) and 9.63 months (95% CI: 7.62-11.24), respectively.
Quantifiable tumor PD-L1 expression was detected in 90.5% of patients in the nivolumab group and 91% of patients in the docetaxel group. Tumor PD-L1 expression levels were balanced across the two treatment groups (nivolumab vs docetaxel) across predefined tumor PD-L1 expression levels, <1% (45.1% vs. 44.4%) and ≥1% (54.9 vs. 55.6%).
Nivolumab was shown to be more likely to improve survival than docetaxel in all defined tumor PD-L1 expression subgroups