Durvalumab injection for treatment of various lung, bladder, liver, and other cancers

Durvalumab is a monoclonal antibody used to treat multiple types of cancer. It is given as an intravenous injection and works by targeting the PD-L1 protein to help the immune system recognize and attack cancer cells. Durvalumab is approved as a single agent or in combination with other therapies for lung cancers, bladder cancers, liver cancer, endometrial cancer, gastric cancer, and biliary tract cancer.

Durvalumab is indicated for adult patients in the following cases:

• Resectable non-small cell lung cancer (NSCLC) (tumors ≥ 4 cm and/or node positive) without EGFR mutations or ALK rearrangements, given as neoadjuvant treatment with platinum-based chemotherapy followed by adjuvant monotherapy post-surgery.
• Unresectable Stage III NSCLC whose disease has not progressed after concurrent platinum-based chemotherapy and radiation therapy (single agent).
• Metastatic NSCLC without sensitizing EGFR or ALK genomic aberrations, in combination with tremelimumab and platinum-based chemotherapy.
• Limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (single agent).
• Extensive-stage small cell lung cancer (ES-SCLC), combined with etoposide and carboplatin or cisplatin, as first-line treatment.
• Locally advanced or metastatic biliary tract cancer (BTC) in combination with gemcitabine and cisplatin.
• Unresectable hepatocellular carcinoma (uHCC) in combination with tremelimumab.
• Primary advanced or recurrent mismatch repair deficient (dMMR) endometrial cancer, combined with carboplatin and paclitaxel chemotherapy.
• BCG-naive, high-risk non-muscle-invasive bladder cancer (NMIBC) in combination with Bacillus Calmette-Guérin (BCG).
• Muscle invasive bladder cancer (MIBC), as neoadjuvant with gemcitabine and cisplatin followed by adjuvant monotherapy after radical cystectomy.
• Resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC) in combination with FLOT chemotherapy as neoadjuvant and adjuvant treatment followed by monotherapy.

Durvalumab

Durvalumab is a human monoclonal antibody that binds to programmed death-ligand 1 (PD-L1), a protein expressed on tumor cells and immune cells. By blocking PD-L1, durvalumab prevents it from binding to PD-1 receptors on T-cells, thereby enabling the immune system to detect and attack cancer cells more effectively.

Durvalumab is administered by intravenous infusion over 60 minutes after dilution.

Dosage by indication and patient weight:

• Resectable NSCLC (neoadjuvant plus adjuvant): For patients ≥ 30 kg, 1,500 mg every 3 weeks with chemotherapy for up to 4 cycles before surgery, then 1,500 mg every 4 weeks as single agent for up to 12 cycles after surgery. For
• Unresectable Stage III NSCLC: ≥ 30 kg, 10 mg/kg every 2 weeks or 1,500 mg every 4 weeks;
• Metastatic NSCLC (with tremelimumab and platinum-chemo): ≥ 30 kg, 1,500 mg every 3 weeks for 4 cycles then 1,500 mg every 4 weeks alone with pemetrexed maintenance;
• Limited-stage SCLC: ≥ 30 kg, 1,500 mg every 4 weeks;
• Extensive-stage SCLC: ≥ 30 kg, 1,500 mg every 3 weeks with chemotherapy for 4 cycles, then 1,500 mg every 4 weeks;
• Biliary tract cancer: ≥ 30 kg, 1,500 mg every 3 weeks with chemo for up to 8 cycles, then 1,500 mg every 4 weeks;
• Unresectable hepatocellular carcinoma: ≥ 30 kg, 1,500 mg with single-dose tremelimumab 300 mg (Day 1, cycle 1), then 1,500 mg every 4 weeks;
• dMMR endometrial cancer: ≥ 30 kg, 1,120 mg with carboplatin/paclitaxel every 3 weeks for 6 cycles, then 1,500 mg every 4 weeks alone;
• BCG-naive high-risk NMIBC: ≥ 30 kg, 1,500 mg every 4 weeks for 13 cycles with BCG;
• Muscle invasive bladder cancer (neoadjuvant/adjuvant): ≥ 30 kg, 1,500 mg every 3 weeks with gemcitabine and cisplatin for 4 cycles before surgery, then 1,500 mg every 4 weeks for up to 8 cycles;
• Resectable gastric or gastroesophageal junction cancer: ≥ 30 kg, 1,500 mg every 4 weeks with FLOT chemotherapy (2 pre-surgery cycles, 2 post-surgery), followed by 1,500 mg alone every 4 weeks up to 10 cycles;

For adverse events, generally withhold durvalumab for severe (Grade 3) immune-mediated reactions and permanently discontinue for life-threatening (Grade 4) or recurrent severe reactions requiring systemic immunosuppression.

Imfinzi (durvalumab) Injection, Solution

No contraindications have been identified for Imfinzi in any of its indicated formulations or uses, including intravenous injection for multiple cancer types. Treatment with Imfinzi is not contraindicated in any specific patient group, strength, or combination regimen based on the official DailyMed prescribing information.

Important precautions and warnings:

• Immune-mediated adverse reactions: Durvalumab can cause inflammation in organs such as lungs (pneumonitis), colon (colitis), liver (hepatitis), kidneys (nephritis), endocrine glands (endocrinopathies), skin (severe dermatitis like Stevens-Johnson syndrome), myocarditis, and neurological toxicity. These may require corticosteroids and withholding or discontinuation of durvalumab.
• Infusion-related reactions: Mild to moderate reactions may need slowing or interrupting infusion. Severe reactions require permanent discontinuation.
• Monitor carefully: Liver enzymes, kidney function, thyroid and other hormone levels, respiratory symptoms, and skin changes during treatment.
• Dosage adjustment: Withhold or permanently discontinue durvalumab depending on severity and response to treatment of immune-mediated adverse events.

Durvalumab treatment may cause various side effects, including but not limited to:

• Common reactions: Infusion-related reactions such as fever, chills, rash, fatigue, nausea, and pruritus.
• Immune-related adverse events: Pneumonitis, colitis, hepatitis, nephritis, endocrinopathies, severe dermatologic reactions like Stevens-Johnson syndrome, myocarditis, and neurological toxicity. Severity ranges from mild to life-threatening.

Durvalumab is often used in combination with other anticancer agents such as platinum-based chemotherapy, etoposide, gemcitabine, carboplatin, cisplatin, paclitaxel, tremelimumab, pemetrexed, BCG, and FLOT chemotherapy regimen. Administration requires separate intravenous infusions with recommended sequences and timing. No direct dose adjustments for durvalumab are recommended for these combinations; however, consider potential overlapping toxicities.

Store durvalumab vials refrigerated at 2°C to 8°C (36°F to 46°F). Do not freeze or shake the vial. Prepare infusion solution by diluting to a concentration between 1 mg/mL and 15 mg/mL in 0.9% Sodium Chloride Injection or 5% Dextrose Injection. Infusion solution should be used immediately or stored up to 28 days refrigerated or up to 8 hours at room temperature before administration.