An introduction to Atezolizumab (Tecentriq®) and its common usage and dosage.👀👀👀

Programmed death ligand 1 (PD-L1) may be expressed on tumor cells and/or tumor-infiltrating immune cells. It promotes the suppression of antitumor immune responses in the tumor microenvironment. PD-L1 binds to the PD-1 and B7.1 receptors on T cells and antigen-presenting cells. The activity, proliferation and cytokine production of cytotoxic T cells are thereby inhibited. Atezolizumab is a monoclonal antibody. It binds to PD-L1, blocking its interaction with PD-1 and B7.1 receptors. Therefore, PD-L1/PD-1-mediated suppression of immune responses is released. This includes activating anti-tumor immune responses without inducing antibody-dependent cellular cytotoxicity. Atezolizumab (Tecentriq®) inhibits tumor growth and improves tumor immunogenicity.

Common Usage and Dosage of Atezolizumab:

Small cell lung cancer (SCLC): Atezolizumab combined with carboplatin and etoposide as first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC). 

• Recommended Usage-1: On the first day of the induction phase, atezolizumab 1200 mg is administered intravenously, followed by carboplatin and finally etoposide. Etoposide was given intravenously on the second and third days. This regimen was administered once every three weeks for a total of four treatment cycles. The induction phase is followed by a chemotherapy-free maintenance phase. During the maintenance phase, atezolizumab was administered as an intravenous infusion of 1200 mg every three weeks.
• Recommended Usage-2: Atezolizumab is administered intravenously once every two weeks, 840 mg each time. Or once every three weeks, 1200 mg each time. Or once every four weeks, 1680 mg each time. If chemotherapy is needed on the same day as atezolizumab injection, it should be given before chemotherapy.
• Duration: Until disease progression or unacceptable toxicity.
• Delayed or missed medication: If a dose is missed on the scheduled day, the dose should be given as soon as possible. The dosing schedule should also be adjusted so that the two doses are separated by three weeks.
• The safety and effectiveness of atezolizumab for the treatment of small cell lung cancer in pediatric patients younger than 18 years of age have not been established.

Hepatocellular Carcinoma (HCC): Atezolizumab combined with bevacizumab for the treatment of patients with unresectable HCC who have not received prior systemic therapy.

• Recommended Usage-1: Atezolizumab (recommended dose 1200 mg) is first intravenously infused, followed by bevacizumab 15 mg/kg intravenously, once every three weeks.
• Recommended Usage-2: Once every two weeks, 840 mg each time. Or once every three weeks, 1200 mg each time. Or once every four weeks, 1680 mg each time. If patients need to receive bevacizumab on the same day, atezolizumab should be administered before bevacizumab. (Bevacizumab once every three weeks, 15 mg/kg each time)
• Duration: May continue until disease progression or unacceptable toxicity.
• Delayed or missed medication: If a dose is missed on the scheduled day, the dose should be given as soon as possible. The dosing schedule should also be adjusted so that the two doses are separated by three weeks.
• The safety and effectiveness of atezolizumab for the treatment of hepatocellular carcinoma in pediatric patients younger than 18 years of age have not been established.

Non-Small Cell Lung Cancer (NSCLC): Atezolizumab can be used alone or in combination with pemetrexed and platinum chemotherapy to treat metastatic non-squamous NSCLC that is negative for epidermal growth factor receptor (EGFR) gene mutations and negative for anaplastic lymphoma kinase (ALK). Patients with stage II to IIIA NSCLC were selected for atezolizumab monotherapy based on PD-L1 expression on tumor cells. Select patients with first-line metastatic NSCLC for atezolizumab as monotherapy based on PD-L1 expression on tumor cells or tumor-infiltrating immune cells.

• Monotherapy dosage: The recommended dose is 1200 mg of atezolizumab administered intravenously once every three weeks until clinical benefit disappears or unacceptable toxicity occurs.
• Combination dose: When atezolizumab is used in combination with carboplatin or cisplatin and pemetrexed, 1200 mg of atezolizumab is infused intravenously on the first day of the induction phase, followed by 500 mg/m2 of pemetrexed intravenously, and finally carboplatin 6 mg/ml/min or cisplatin 75 mg/m2, administered once every three weeks for a total of four or six treatment cycles. The patients were then treated with a maintenance phase of atezolizumab 1200 mg and pemetrexed 500 mg/m2 intravenously every three weeks. Treatment continued until loss of clinical benefit or unacceptable toxicity occurred.
• Delayed or missed medication: If a dose is missed on the scheduled day, the dose should be given as soon as possible. The dosing schedule should also be adjusted so that the two doses are separated by three weeks.
• The safety and effectiveness of atezolizumab for the treatment of NSCLC in pediatric patients younger than 18 years of age have not been established.

Melanoma: Atezolizumab in combination with cobimetinib and vemurafenib is used to treat adult patients with BRAF V600 mutation-positive unresectable or metastatic melanoma.

• Recommended dose: Atezolizumab is administered as an intravenous infusion of 840 mg once every two weeks, or 1200 mg once every three weeks, or 1680 mg once every four weeks. At the same time, take 60 mg of cobimetinib orally once a day (take the medicine for 21 days and rest for 7 days) and take 720 mg of vemurafenib orally twice a day. Treatment was until disease progression or unacceptable toxicity.
• Before starting atezolizumab treatment, patients should receive a 28-day oral treatment cycle of cobimetinib and vemurafenib: 60 mg of cobimetinib once daily (21 days of treatment followed by 7 days of rest). and 960 mg of vemurafenib twice daily (Days 1 to 21), followed by 720 mg of vemurafenib twice daily (Days 22 to 28).
• The safety and effectiveness of atezolizumab for the treatment of melanoma in pediatric patients younger than 18 years of age have not been established.

Alveolar soft part sarcoma (ASPS): Atezolizumab is indicated as a monotherapy for the treatment of unresectable or metastatic ASPS.

• Usual dosage for adults: Atezolizumab 840 mg once every two weeks, or 1200 mg once every three weeks, or 1680 mg once every four weeks. Treatment was until disease progression or unacceptable toxicity.
• Usual dose for children: Atezolizumab can also be used as a single agent to treat unresectable or metastatic ASPS in children 2 years and older. 15 mg/kg once every three weeks, maximum dose is 1200 mg. Treatment was until disease progression or unacceptable toxicity.

The initial intravenous infusion should last at least 60 minutes. If the patient tolerates the first infusion well, the duration of subsequent infusions can be shortened appropriately, but should continue for at least 30 minutes.

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An introduction to Avelumab (Bavencio®) and its common usage and dosage.👀👀👀

Avelumab (Bavencio®): It is a Programmed Death Ligand 1 (PD-L1) inhibitor that was first approved by the FDA in 2017. Programmed Death Ligand 1 is expressed on tumor cells and immune cells infiltrating tumors. It suppresses anti-tumor immunity in the tumor microenvironment. PD-1 and B7.1 receptors on T cells and antigen-presenting cells bind to PD-L1. They inhibit cytotoxic T-cell activity, T-cell proliferation, and cytokine production. The binding of avelumab to PD-L1 will prevent PD-L1 from interacting with PD-1 and B7.1 receptors. Therefore, it can restore immune responses, including anti-tumor immune responses. In in vitro studies, avelumab induced antibody-dependent cell-mediated cytotoxicity (ADCC). Blocking PD-L1 activity has also been shown to reduce tumor growth in mouse tumor models.

Common Usage and Dosage of Avelumab:

Metastatic Merkel cell carcinoma (MCC): Avelumab can be used in patients 12 years of age and older with metastatic Merkel cell carcinoma. It is recommended for intravenous infusion of 800 mg every two weeks (infusion time is 60 minutes) until disease progression or unacceptable toxicity occurred.

Locally advanced or metastatic urothelial carcinoma (UC): Avelumab is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have not progressed on first-line platinum-containing chemotherapy. It is also indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed during or after platinum-containing chemotherapy, and for patients with locally advanced or metastatic urothelial carcinoma whose disease has progressed within 12 months of neo-adjuvant or adjuvant treatment with platinum-containing chemotherapy. It is recommended for intravenous infusion of 800 mg every two weeks (infusion time is 60 minutes) until disease progression or unacceptable toxicity occurred.

Advanced Renal Cell Carcinoma (RCC): Avelumab can be used in combination with axitinib as a first-line treatment for patients with advanced RCC. It is recommended to be administered by intravenous infusion of 800 mg (infusion time is 60 minutes) every two weeks in combination with oral axitinib 5 mg (twice daily, 12 hours apart, with or without food) until disease progression or unacceptable toxicity occurred. When used in combination with axitinib, it may be considered to increase axitinib to above 5 mg every two weeks or longer intervals. However, before adjusting the dose, the relevant physiological indicators of axitinib should be reviewed. 

The recommended dose for children 12 years and older is the same as that for adults. However, the safety and efficacy of avelumab in patients younger than 12 years of age have not yet been established.

Administration of Avelumab:

Before the first four infusions of avelumab, patients were given antihistamines and acetaminophen. Subsequent Avelumab treatment requires prophylactic medication based on previous injection reactions, severity and clinical judgment.

Common adverse reactions:

• Gastrointestinal disorders: abdominal pain, constipation, diarrhea, nausea, vomiting.
• General disorders: fatigue, infusion-related reactions, peripheral edema.
• Metabolic and nutritional disorders: decreased appetite and weight loss.
• Musculoskeletal and Connective Tissue Disorders: arthralgia, musculoskeletal pain.
• Nervous system disorders: dizziness, headache.
• Respiratory, thoracic and mediastinal disorders: cough, dyspnea.
• Skin and subcutaneous tissue disorders: itching, rash.
• Vascular disease: hypertension.
• Laboratory index changes: anemia, hyperglycemia, increased aspartate aminotransferase (AST), increased alanine aminotransferase (ALT), increased lipase, increased amylase, increased bilirubin, lymphocytopenia, neutropenia, thrombocytopenia.

Serious adverse reactions:

• Blood disorders: anemia.
• Cardiovascular disease: hypertension.
• Gastrointestinal diseases: abdominal pain, intestinal obstruction.
• Infections: cellulitis, sepsis.
• Kidney disease: acute kidney injury, hematuria, urinary tract infection.
• Respiratory disorders: difficulty breathing.

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