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.

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.

FUNDING: AstraZeneca KK.