This phase 2 platform study (ORCHARD) evaluated durvalumab 1,500 mg IV Q3W plus etoposide-platinum Q3W (up to 4 cycles) in 14 patients with EGFR-mutated advanced NSCLC who developed neuroendocrine transformation (SCLC or large cell neuroendocrine carcinoma) after progression on first-line osimertinib.
Confirmed ORR was 43% (80% CI: 24–63%; 6 partial responses); median DoR 4.3 months; median PFS 4.2 months (95% CI: 3.0–5.6); median OS 10.2 months (95% CI: 4.3–16.8). Grade ≥3 AEs occurred in 64% of patients, most commonly neutropenia.
Extremely small sample size (n=14) limits statistical power and generalizability. Single-arm design with no comparator group. The 80% CI used for the primary ORR endpoint is non-standard and may overstate precision.
Durvalumab plus etoposide-platinum yields a modest response (~43% ORR) in neuroendocrine-transformed EGFR-mutated NSCLC post-osimertinib, but responses are short-lived (median ~4 months) and most patients progress or die within a year. This regimen may serve as a bridge option while better therapies are sought for this rare resistance mechanism.
Explore related topics
