Phase 2 trial of durvalumab plus etoposide-platinum for EGFR-mutated aNSCLC and neuroendocrine transformation after first-line osimertinib

The multinational phase 2 ORCHARD study evaluated resistance mechanisms and post-progression treatments in patients with EGFR-mutated advanced non-small cell lung cancer (aNSCLC) progressing on first-line osimertinib. Results of the module investigating durvalumab plus etoposide-platinum in patients with neuroendocrine transformation to small cell lung cancer or large cell neuroendocrine carcinoma have now been published. Patients received durvalumab 1,500 mg plus etoposide-platinum every three weeks for up to four cycles, followed by durvalumab until progression, unacceptable toxicity or another discontinuation criterion was met. The primary endpoint was investigator-assessed objective response rate (ORR). Among 14 evaluable patients, 6 partial responses were observed, for a confirmed ORR of 43% (80% CI 24-63). Median duration of response was 4.3 months; one patient had a response lasting 10 months. Median progression-free survival was 4.2 months (95% CI 3.0-5.6) and median overall survival was 10.2 months (4.3-16.8). Nine patients (64%) reported grade 3 or higher adverse events, and one patients discontinued all three study drugs due to an adverse event (not treatment-related). The authors conclude that durvalumab plus etoposide-platinum demonstrated a modest treatment response in neuroendocrine-transformed EGFR-mutated NSCLC. No new safety signals were observed.