The U.S. Food and Drug Administration (FDA) has approved the PD-L1 inhibitor durvalumab (Imfinzi) 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 EGFR mutations or ALK rearrangements.
AEGEAN Trial
Efficacy was evaluated in AEGEAN (ClinicalTrials.gov identifier NCT03800134), a randomized, double-blind, placebo-controlled multicenter trial in 802 patients with previously untreated and resectable squamous or nonsquamous NSCLC (stage IIA to select stage IIIB per the American Joint Committee on Cancer, 8th edition). Patients were randomly assigned 1:1 to receive 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 by blinded independent central review assessment and pathological complete response by blinded central pathology review. Median event-free survival was not reached (95% confidence interval [CI] = 31.9 months to not estimable) in the durvalumab arm and 25.9 months (95% CI = 18.9 months to not estimable) in the placebo arm (hazard ratio = 0.68, 95% CI = 0.53–0.88, P = .0039). The pathological complete response 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 was not formally tested for statistical significance; however, a descriptive analysis revealed no clear detriment.
The most common adverse reactions occurring in ≥ 20% of patients who received durvalumab were anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash. Of the patients who received neoadjuvant durvalumab, 1.7% were unable to undergo 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.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
