Durvalumab, carboplatin, and etoposide in patients who are treatment-naive with extensive-stage small-cell lung cancer and poor performance status (NEJ045A): a single-arm phase 2 trial
Mené sur 57 patients atteints d'un cancer du poumon à petites cellules de stade étendu et présentant un faible statut de performance (âge médian : 73,5 ans), cet essai de phase II évalue l'efficacité, du point de vue du taux de survie à 1 an, et la toxicité d'un traitement de première ligne combinant durvalumab, carboplatine et étoposide
Background: Treating patients with extensive-stage small-cell lung cancer (SCLC) with poor performance status poses considerable challenges. We aimed to evaluate the combination of an immune checkpoint inhibitor with platinum-based therapy in this population.
Methods: This open-label, single-arm phase 2 NEJ045A trial enrolled untreated patients with extensive-stage SCLC with performance status 2 or 3. Participants received four cycles of durvalumab, carboplatin, and etoposide, followed by durvalumab maintenance. A dose adjustment strategy was used, with initial reductions in carboplatin–etoposide dosages, subsequently adjusted based on adverse events, allowing for potential escalation. The primary endpoint was tolerability, assessed by the proportion of patients completing induction therapy. A key secondary endpoint was 1-year survival rate. This trial is registered at the Japan Registry of Clinical Trials (jRCTs031200319) and has been completed.
Findings: Between April 8, 2021, and Oct 3, 2023, 57 patients (performance status 2 n=43 and performance status 3 n=14) were enrolled with a median age of 73·5 years (IQR 69·0–77·5), 44 (79%) of 56 were male. 26 (67%; 80% CI 55·2–76·7; p<0·0001) of 39 patients with performance status 2 and five (50%; 26·7–73·3; p=0·0088) of ten with performance status 3 completed induction therapy, exceeding the pre-specified threshold. Grade 3 or higher adverse events occurred in 52 (93%) of 56 patients, and 12 (21%) of 56 discontinued due to adverse events. The 1-year survival rates were 43·4% (80% CI 34·1–53·1) overall (p<0·0001), 50·0% (39·1–60·9) in performance status 2 (p<0·0001), and 18·2% (5·0–41·5) in performance status 3.
Interpretation: Durvalumab, carboplatin, and etoposide showed tolerability and promising efficacy as a first-line treatment for patients with untreated extensive-stage SCLC with poor performance status, supporting the integration of immune checkpoint inhibitors in this therapeutically challenging population.
The Lancet Respiratory Medicine , résumé, 2025