Neoadjuvant-Adjuvant Durvalumab Receives FDA Approval for Resectable Lung Cancer

On August 15, 2024, the FDA (United States Food and Drug Administration) approved durvalumab (Imfinzi, AstraZeneca) and platinum-based chemotherapy for treatment before surgery (neoadjuvant) and after surgery (adjuvant). Durvalumab will be used with chemotherapy before surgery and as monotherapy afterward. This approval covers adults with resectable non-small cell lung cancer (NSCLC; tumor ≥ 4 cm and/or node-positive) whose tumors have no epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

FDA Approval Based on the AEGEAN Trial

Efficacy was evaluated in AEGEAN, a randomized, double-blind, placebo-controlled, multicenter trial involving 802 patients with previously untreated, resectable squamous or nonsquamous NSCLC, from stage IIA to selected stage IIIB. Patients were randomized 1:1 to durvalumab or placebo with platinum-based chemotherapy every 3 weeks for up to 4 cycles (neoadjuvant treatment), followed by durvalumab or placebo every 4 weeks for up to 12 cycles (adjuvant treatment).

The primary efficacy endpoints were event-free survival (EFS), assessed by blinded independent central review, and pCR ( Pathologic Complete Response) rates, assessed by blinded central pathology review.

• Median EFS was not reached in the durvalumab arm (95% CI: 31.9, not estimable [NE]), compared with 25.9 months in the placebo arm (95% CI: 18.9, NE) (hazard ratio 0.68 [95% CI: 0.53, 0.88]; p-value=0.0039).
• The pCR rates in the durvalumab and placebo arms were 17% (95% CI: 13, 21) and 4.3% (95% CI: 2.5, 7), respectively.

Overall survival was not formally tested for statistical significance at the prespecified interim analyses.

Side Effects

The most common treatment-related side effects (20% or more) included anemia, nausea, constipation, fatigue, musculoskeletal pain and rash. Adverse events prevented surgery in 1.7% of patients receiving neoadjuvant durvalumab, compared with 1% in the placebo arm.

Dosage and Administration

For patients weighing ≥ 30 kg, the recommended durvalumab dose is 1,500 mg every 3 weeks during neoadjuvant treatment and every 4 weeks during adjuvant treatment. For patients weighing < 30 kg, the recommended dose is 20 mg/kg. When durvalumab and chemotherapy are given on the same day, durvalumab should be administered first.

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FDA Approvals in Resectable Lung Cancer

With durvalumab's approval, there are now 5 FDA-approved treatment approaches for resectable non-small cell lung cancer. Atezolizumab and pembrolizumab are approved as adjuvant treatments, nivolumab as neoadjuvant treatment, and pembrolizumab and durvalumab as perioperative treatment, both before and after surgery.

Beyond these FDA approvals, CheckMate 77T is expected to support approval of perioperative nivolumab treatment. Results were published in NEJM on May 15, 2024. At a median follow-up of 25.4 months, disease-free survival was 70.2% among patients receiving nivolumab before and after surgery, compared with 50% among those receiving chemotherapy alone.