Osimertinib Plus Platinum-based Chemotherapy in Patients With EGFR-Mutated Advanced NSCLC Post-progression on First-Line Osimertinib: ORCHARD.

Authors

Jonathan W Goldman, Jonathan W Riess, Byoung Chul Cho, Sarah B Goldberg, Xiuning Le, Zofia Piotrowska, Isamu Okamoto, Helena A Yu, Rosario García-Campelo, Javier de Castro Carpeño, Simon Ekman, Noemi Reguart, Marthe S Paats, Sang-We Kim, Yu Jung Kim, Makoto Nishio, Kristen A Marrone, Knut B Smeland, Lizza E L Hendriks, Hiroaki Akamatsu, Junichi Shimizu, Paul E Smith, Kwan Ho Tang, Jonathan M Lehman, Adrianus J de Langen

Published in

Clinical lung cancer. Volume 27. Issue 9. Pages 52-61. Sep 05, 2026. Epub Sep 05, 2026.

Abstract

ORCHARD (NCT03944772) was a biomarker-directed, phase II, platform study conducted to characterize 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.
Patients received osimertinib (80 mg once daily) plus ≤ 4 cycles of platinum-based doublet chemotherapy (pemetrexed 500 mg/m² 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.
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 7 (23%) patients.
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.

PMID:
42913244
Bibliographic data and abstract were imported from PubMed on 24 Oct 2026.

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