The U.S. Food and Drug Administration approved durvalumab combined with platinum-based chemotherapy as a neoadjuvant treatment, followed by single-agent durvalumab as adjuvant therapy, for adults with resectable non–small cell lung cancer with tumors ≥ 4 cm or node-positive disease, excluding those with known epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements.
The approval was based on findings from the AEGEAN trial (NCT03800134), a randomized, double-blind, placebo-controlled study involving 802 patients with previously untreated, resectable squamous or non-squamous non–small cell lung cancer (NSCLC) (stage IIA to selected stage IIIB). Patients were randomized 1:1 to receive either durvalumab or placebo in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles (neoadjuvant phase), followed by either single-agent durvalumab or placebo every 4 weeks for up to 12 cycles (adjuvant phase).
Key efficacy outcomes included event-free survival (EFS) and pathological complete response (pCR). The median EFS was not reached in the durvalumab group (95% confidence interval [CI] = 31.9 months to not estimable [NE]) compared to 25.9 months in the placebo group (95% CI = 18.9 months to NE; hazard ratio = 0.68; 95% CI = 0.53–0.88; p=0.0039). The pCR rate was 17% (95% CI = 13%–21%) in the durvalumab arm compared to 4.3% (95% CI = 2.5%–7%) in the placebo arm. Interim analysis of overall survival did not show a significant difference between the groups.
Common adverse reactions (occurring in ≥ 20% of patients receiving the agent) included anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash. In the neoadjuvant phase, 1.7% of patients in the durvalumab group were unable to undergo surgery due to adverse reactions, compared to 1% in the placebo group.
The recommended durvalumab dosage for patients weighing ≥ 30 kg is 1,500 mg every 3 weeks (neoadjuvant) and every 4 weeks (adjuvant). For those weighing < 30 kg, the dosage is 20 mg/kg.
Citation:
U.S. Food and Drug Administration. FDA approves durvalumab for resectable non-small cell lung cancer. FDA. August 15, 2024. Accessed August 16, 2024. https://www.fda.gov/drugs/news-events/fda-approves-durvalumab-resectable-non-small-cell-lung-cancer