What is the recommended use and dosage of Imfinzi (durvalumab) for cancer treatment?

Imfinzi (Durvalumab): Recommended Use and Dosage for Cancer Treatment

Imfinzi (durvalumab) is FDA-approved for multiple cancer indications with specific dosing regimens: 1,500 mg IV every 3-4 weeks depending on the indication, or 20 mg/kg for patients <30 kg, with treatment durations ranging from 12 months (consolidation therapy) to 24 months (metastatic disease) or until disease progression. 1

FDA-Approved Indications and Dosing

Stage III Non-Small Cell Lung Cancer (NSCLC) - Consolidation Therapy

• Administer durvalumab 1,500 mg IV every 4 weeks for up to 12 months in patients with unresectable stage III NSCLC who have not progressed following platinum-based concurrent chemoradiotherapy 2, 1
• Initiate treatment 1-42 days after completing chemoradiotherapy to maximize benefit 2
• This represents a Category 1, Level A recommendation with strong evidence showing median overall survival of 47.5 months versus 29.1 months with placebo (HR 0.72) 2
• The 5-year overall survival rate is 42.9% versus 33.4% with placebo, establishing this as standard of care 2
• Grade 3-4 pneumonitis occurs in only 4.4% of patients, making this a manageable toxicity profile 2

Resectable NSCLC - Perioperative Treatment

• Neoadjuvant phase: Durvalumab 1,500 mg IV every 3 weeks for 4 cycles in combination with platinum-based chemotherapy prior to surgery 1, 3
• Adjuvant phase: Durvalumab 1,500 mg IV every 4 weeks for 12 cycles as monotherapy after surgery 1, 3
• For patients <30 kg: Use 20 mg/kg at the same intervals 1
• This perioperative approach achieves 17.2% pathologic complete response versus 4.3% with chemotherapy alone (P<0.001) 3
• Event-free survival benefit is observed regardless of PD-L1 expression or disease stage 3

Extensive-Stage Small Cell Lung Cancer (SCLC)

• Durvalumab 1,500 mg IV every 3 weeks for 4 cycles in combination with platinum (carboplatin or cisplatin) plus etoposide, followed by durvalumab maintenance every 4 weeks until disease progression 2, 1
• This is a Category 1, Level A recommendation with median overall survival of 12.9 months versus 10.5 months with chemotherapy alone (HR 0.75) 2
• The 18-month overall survival rate is 32.0% versus 24.8% with chemotherapy alone 2
• Only offer to patients with ECOG performance status 0-1 and asymptomatic or treated brain metastases, as these were the trial inclusion criteria 2

Limited-Stage Small Cell Lung Cancer (LS-SCLC) - Consolidation

• Durvalumab 1,500 mg IV every 4 weeks for up to 24 months as consolidation therapy after concurrent chemoradiotherapy without disease progression 2
• Initiate 1-42 days after completing chemoradiotherapy 2
• This achieves 2-year overall survival of 68% versus 58.5% with placebo (HR 0.73) 2
• The median overall survival is 55.9 months versus 33.4 months with placebo 2

Metastatic NSCLC - First-Line Combination Therapy

• Durvalumab 1,500 mg IV every 3 weeks for 4 cycles in combination with tremelimumab 75 mg and platinum-based chemotherapy, followed by durvalumab 1,500 mg every 4 weeks as maintenance 1
• For patients <30 kg: Durvalumab 20 mg/kg and tremelimumab 1 mg/kg 1
• Chemotherapy regimen selection depends on histology:
  • Non-squamous: Carboplatin/pemetrexed, cisplatin/pemetrexed, or carboplatin/nab-paclitaxel 1
  • Squamous: Carboplatin/gemcitabine, cisplatin/gemcitabine, or carboplatin/nab-paclitaxel 1
• Continue durvalumab maintenance until disease progression or unacceptable toxicity 1

Endometrial Cancer (dMMR)

• Durvalumab 1,120 mg IV every 3 weeks for 6 cycles in combination with carboplatin and paclitaxel, followed by durvalumab 1,500 mg every 4 weeks as maintenance 1
• For patients <30 kg: Durvalumab 15 mg/kg during combination phase, then 20 mg/kg during maintenance 1
• Continue until disease progression or unacceptable toxicity 1

Administration Guidelines

Infusion Parameters

• Administer as 60-minute IV infusion after dilution 1
• Weigh patients prior to each infusion to ensure accurate dosing for weight-based regimens 1
• When combining with chemotherapy, administer durvalumab prior to chemotherapy on the same day 1
• When combining with tremelimumab, administer tremelimumab prior to durvalumab on the same day 1

Dosage Modifications

• No dose reductions are recommended for durvalumab 1
• Withhold durvalumab for Grade 3 immune-mediated adverse reactions 1
• Permanently discontinue for:
  • Grade 4 immune-mediated adverse reactions 1
  • Recurrent Grade 3 immune-mediated reactions requiring systemic immunosuppression 1
  • Inability to reduce corticosteroids to ≤10 mg prednisone equivalent daily within 12 weeks 1

Special Populations and Clinical Considerations

Sequential Chemoradiotherapy in Stage III NSCLC

• For patients who received sequential (rather than concurrent) chemoradiotherapy, durvalumab demonstrates similar safety with 6.0% Grade 3-4 possibly related adverse events 4
• Median overall survival is 39.0 months with 3-year survival rate of 56.5% 4
• This represents a viable alternative when concurrent chemoradiotherapy is not feasible 4

Chemotherapy-Ineligible Stage III NSCLC

• For patients ineligible for chemotherapy who receive radiotherapy alone, durvalumab consolidation shows 9.8% Grade 3-4 possibly related adverse events within 6 months 5
• Median overall survival is 21.1 months with 12-month survival rate of 64.7% 5
• This applies to frailer, older patients (median age 79 years) with ECOG performance status 0-2 5

Patients with Interstitial Lung Disease

• Durvalumab can be used cautiously in NSCLC patients with pre-existing interstitial lung disease, as pneumonitis rates are predominantly low-grade 6
• Close monitoring is essential, though successful treatment with durable responses has been documented 6

Critical Exclusions and Contraindications

Molecular Subgroups

• Insufficient evidence exists to recommend durvalumab consolidation in patients with EGFR mutations or ALK rearrangements following concurrent chemoradiotherapy for stage III NSCLC 2
• Post-hoc analysis suggests lack of benefit in PD-L1-negative tumors (HR 1.05), though this represents only 20% of the trial population 2
• In perioperative trials, data from 62 patients with EGFR/ALK alterations were excluded from efficacy analyses 3

Performance Status Requirements

• For extensive-stage SCLC, only patients with ECOG PS 0-1 should receive durvalumab, as trials excluded PS 2 patients 2
• Median age in SCLC trials was relatively low (62-64 years), limiting generalizability to older, frailer populations 2

Common Pitfalls to Avoid

• Do not delay durvalumab initiation beyond 42 days after completing chemoradiotherapy in stage III NSCLC, as this was the trial protocol limit 2
• Do not use prophylactic cranial irradiation in stage III NSCLC patients receiving durvalumab consolidation, as there is no established role 2
• Do not assume PD-L1 testing is required for treatment decisions in extensive-stage SCLC, as benefits are consistent across PD-L1 subgroups 2
• Do not continue durvalumab beyond 12 months in stage III NSCLC consolidation or beyond 24 months in limited-stage SCLC, as these were the protocol-defined durations 2, 1