Atezolizumab

【Indications】

Atezolizumab (TECENTRIQ) is a programmed death-ligand 1 (PD-L1) blocking antibody indicated for the treatment of adult patients with:

Urothelial Carcinoma

Locally advanced or metastatic urothelial carcinoma:

• In patients ineligible for cisplatin-containing chemotherapy whose tumors express PD-L1 [PD-L1 stained tumor-infiltrating immune cells (IC) covering ≥5% of the tumor area], or

• In patients ineligible for any platinum-containing chemotherapy, regardless of PD-L1 status.

Non-Small Cell Lung Cancer (NSCLC)

• Adjuvant treatment following resection and platinum-based chemotherapy in patients with Stage II-IIIA NSCLC whose tumors express PD-L1 ≥1%.

• First-line treatment of adult patients with metastatic NSCLC whose tumors have high PD-L1 expression [PD-L1 stained tumor cells (TC) ≥50% or PD-L1 stained IC covering ≥10% of the tumor area (IC≥10%)] and no EGFR or ALK genomic aberrations.

• In combination with bevacizumab, paclitaxel, and carboplatin for first-line treatment of adult patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic aberrations.

• In combination with albumin-bound paclitaxel and carboplatin for first-line treatment of adult patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic aberrations.

• Adult patients with metastatic NSCLC whose disease progressed during or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic aberrations should have disease progression after FDA-approved therapy prior to receiving atezolizumab.

Small Cell Lung Cancer (SCLC)

In combination with carboplatin and etoposide for first-line treatment of adult patients with extensive-stage SCLC.

Hepatocellular Carcinoma (HCC)

In combination with bevacizumab for the treatment of patients with unresectable or metastatic HCC who have not received prior systemic therapy.

Melanoma

In combination with cobimetinib and vemurafenib for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma.

【Recommended Dosage】

The first intravenous infusion should be administered over at least 60 minutes. If the first infusion is well tolerated, subsequent infusions may be given over at least 30 minutes.

Urothelial Carcinoma

As a single agent: 840 mg every 2 weeks; or 1200 mg every 3 weeks; or 1680 mg every 4 weeks.

Non-Small Cell Lung Cancer

• Adjuvant: 840 mg every 2 weeks; or 1200 mg every 3 weeks; or 1680 mg every 4 weeks for up to 1 year. Platinum-based chemotherapy for a maximum of 4 cycles.

• Metastatic: 840 mg every 2 weeks; or 1200 mg every 3 weeks; or 1680 mg every 4 weeks.

  When used with chemotherapy with or without bevacizumab, administer atezolizumab prior to chemotherapy and bevacizumab.

Small Cell Lung Cancer

840 mg every 2 weeks; or 1200 mg every 3 weeks; or 1680 mg every 4 weeks. When used with carboplatin and etoposide, administer atezolizumab prior to chemotherapy.

Hepatocellular Carcinoma

840 mg every 2 weeks; or 1200 mg every 3 weeks; or 1680 mg every 4 weeks. If bevacizumab is administered on the same day, give atezolizumab first.

Melanoma

Following completion of the first 28-day cycle of cobimetinib and vemurafenib: Atezolizumab 840 mg every 2 weeks; or 1200 mg every 3 weeks; or 1680 mg every 4 weeks, in combination with cobimetinib 60 mg orally once daily (21 days on/7 days off) and vemurafenib 720 mg orally twice daily.

【Adverse Reactions】

• Most common (≥20%) as a single agent: Fatigue/asthenia, nausea, cough, dyspnea, decreased appetite.

• Most common (≥20%) in combination for NSCLC and SCLC: Fatigue/asthenia, nausea, alopecia, constipation, diarrhea, decreased appetite.

• Most common (≥20%) in combination with bevacizumab for HCC: Hypertension, fatigue, proteinuria.

• Most common (≥20%) in combination with cobimetinib and vemurafenib for Melanoma: Rash, musculoskeletal pain, fatigue, hepatotoxicity, pyrexia, nausea, pruritus, edema, stomatitis, hypothyroidism, photosensitivity reaction.

【Pharmacological Action】

Atezolizumab is a monoclonal antibody that binds specifically to PD-L1. PD-L1 is expressed on tumor cells and tumor-infiltrating immune cells, contributing to the suppression of antitumor immune responses within the tumor microenvironment. Binding of PD-L1 to PD-1 and B7.1 receptors on T cells and antigen-presenting cells inhibits cytotoxic T-cell activity, T-cell proliferation, and cytokine release.

Atezolizumab blocks the interaction of PD-L1 with PD-1 and B7.1, thereby counteracting PD-L1/PD-1-mediated immune suppression, including reactivation of antitumor immune responses without inducing antibody-dependent cellular cytotoxicity. In syngeneic mouse tumor models, blockade of PD-L1 activity resulted in slowed tumor growth.

【Storage】

Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.

Do not freeze.

Do not shake.