FDA approves neoadjuvant/adjuvant durvalumab for resectable non-small cell lung cancer

On August 15, 2024, the Food and Drug Administration approved durvalumab (Imfinzi, AstraZeneca) with platinum-containing chemotherapy as neoadjuvant treatment, followed by single-agent durvalumab as adjuvant treatment after surgery for adults with resectable (tumors ≥ 4 cm and/or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

Full prescribing information for Imfinzi will be posted on Drugs@FDA. 

Efficacy and Safety

Efficacy was evaluated in AEGEAN (NCT03800134), a randomized, double-blind, placebo-controlled multicenter trial in 802 patients with previously untreated and resectable squamous or non-squamous NSCLC (Stage IIA to select Stage IIIB [AJCC, 8th edition]). Patients were randomized (1:1) to either durvalumab or placebo, with platinum-based chemotherapy, every 3 weeks for up to 4 cycles (neoadjuvant treatment) followed by either continued single-agent durvalumab or placebo, every 4 weeks for up to 12 cycles (adjuvant treatment). 

The major efficacy outcome measures were event-free survival (EFS) by blinded independent central review assessment and pathological complete response (pCR) by blinded central pathology review. Median EFS was not reached (95% CI: 31.9, not estimable [NE]) in the durvalumab arm and 25.9 months (95% CI: 18.9, NE) in the placebo arm (hazard ratio 0.68 [95% CI: 0.53, 0.88]; p-value=0.0039). The pCR rate was 17% (95% CI: 13, 21) and 4.3% (95% CI: 2.5, 7) in the durvalumab and placebo arms, respectively.  At the time of the prespecified interim analyses, overall survival (OS) was not formally tested for statistical significance; however, a descriptive analysis revealed no clear detriment.

The most common adverse reactions (≥20%) were anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash. Of the patients who received neoadjuvant durvalumab, 1.7% were unable to receive surgery due to adverse reactions compared with 1% in the placebo arm. 

For patients with a body weight of ≥ 30 kg, the recommended durvalumab dosage is 1,500 mg every 3 weeks (neoadjuvant treatment) and every 4 weeks (adjuvant treatment). For patients with a body weight of < 30 kg, the recommended durvalumab dosage is 20 mg/kg. Durvalumab should be administered prior to chemotherapy when administered on the same day.

Expedited Programs

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.