FDA Greenlights Durvalumab for NSCLC

On August 15, 2024, the Food and Drug Administration (FDA) approved the use of durvalumab (Imfinzi, AstraZeneca) in combination with platinum-containing chemotherapy as a neoadjuvant treatment for adults with resectable non-small cell lung cancer (NSCLC). This regimen is followed by single-agent durvalumab as adjuvant therapy after surgery. The approval specifically targets patients with resectable tumors (≥4 cm and/or node-positive) who do not have known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

Efficacy and Safety

The efficacy of this treatment combination was assessed in the AEGEAN trial (NCT03800134), a randomized, double-blind, placebo-controlled multicenter study involving 802 patients with previously untreated, resectable squamous or non-squamous NSCLC (Stage IIA to select Stage IIIB [AJCC, 8th edition]). Participants were randomized to receive either durvalumab or placebo alongside platinum-based chemotherapy every 3 weeks for up to 4 cycles (neoadjuvant phase), followed by continued treatment with durvalumab or placebo every 4 weeks for up to 12 cycles (adjuvant phase).

The primary efficacy endpoints were event-free survival (EFS) and pathological complete response (pCR), evaluated by blinded independent review. The median EFS was not reached (95% CI: 31.9, not estimable [NE]) in the durvalumab group compared to 25.9 months (95% CI: 18.9, NE) in the placebo group, with a hazard ratio of 0.68 (95% CI: 0.53, 0.88; p-value=0.0039). The pCR rate was 17% (95% CI: 13, 21) for the durvalumab arm and 4.3% (95% CI: 2.5, 7) for the placebo arm. Although overall survival (OS) was not formally analyzed for statistical significance at this stage, descriptive data indicated no adverse trends.

Common adverse reactions (≥20%) associated with durvalumab included anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash. Among those receiving neoadjuvant durvalumab, 1.7% were unable to proceed with surgery due to adverse reactions, compared to 1% in the placebo group.

The recommended dosage for durvalumab is 1,500 mg every 3 weeks for neoadjuvant treatment and every 4 weeks for adjuvant treatment for patients weighing ≥30 kg. For patients weighing <30 kg, the recommended dosage is 20 mg/kg. Durvalumab should be administered before chemotherapy when given on the same day. Full prescribing information for Imfinzi will be available on Drugs@FDA.

Highlights

• FDA approves durvalumab with platinum chemotherapy as neoadjuvant treatment for resectable NSCLC.
• Single-agent durvalumab is used as adjuvant therapy following surgery.
• AEGEAN trial shows significant improvement in event-free survival and pathological complete response with durvalumab.
• Common adverse reactions include anemia, nausea, and fatigue; slight increase in surgery-related issues compared to placebo.
• Dosage recommendations vary based on body weight and should precede chemotherapy when administered together.

Data Source: https://www.fda.gov/news-events/press-announcements/fda-roundup-august-16-2024