Work

Osimertinib plus platinum-based chemotherapy in patients with EGFR-mutated advanced NSCLC post-progression on first-line osimertinib: ORCHARD

Year: 2026

Type: article

Abstract: Background ORCHARD (NCT03944772) was a biomarker-directed, phase II, platform study conducted to characterise resistance mechanisms and evaluate novel treatment combinations in patients with epidermal growth factor receptor ( EGFR )-mutated non-small cell lung cancer (NSCLC) following progression on first-line osimertinib. We report results from the module evaluating osimertinib plus platinum-based chemotherapy. Methods Patients received osimertinib (80 mg once daily) plus ≤ 4 cycles of platinum-based doublet chemotherapy (pemetrexed 500 mg/m 2 plus carboplatin AUC5) on day 1 of every 21-day cycle, followed by pemetrexed maintenance until disease progression, unacceptable toxicity, or another discontinuation criterion. The primary endpoint was objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints were progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety. Results Thirty-one patients received study treatment. Eight patients had a confirmed partial response (ORR 26 %; 80 % CI, 16–39). Median DoR was 7.6 months (95 % CI, 4.2–not calculable). Median PFS was 5.6 months (95 % CI, 4.0–7.5); PFS events were reported in 29 (94 %) patients. Median OS was 10.9 months (95 % CI, 8.5–15.0); 20 (65 %) patients had died at data cut-off. Grade ≥ 3 adverse events (AEs) occurred in 20 (65 %) patients; AEs leading to discontinuation of any treatment occurred in seven (23 %) patients. Conclusion In patients with EGFR -mutated advanced NSCLC who had progressed on first-line osimertinib, osimertinib plus platinum-based chemotherapy demonstrated a modest clinical benefit and manageable safety profile, consistent with the individual drug profiles.

Source: Clinical Lung Cancer

DOI: 10.1016/j.cllc.2026.09.001