Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2023
Osimertinib treatment based on plasma T790M monitoring in patients with EGFR-mutant non-small-cell lung cancer (NSCLC): EORTC Lung Cancer Group 1613 APPLE phase II randomized clinical trial.
Trial report in Annals of oncology : official journal of the European Society for Medical Oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Prognostic utility of circulating tumor DNA assessment in immune checkpoint inhibitor-treated advanced non-small cell lung cancer: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- Is there a room for radical salvage resection in initially-unresectable non-small cell lung cancer patients after EGFR-TKI based therapy?Translational lung cancer research · 2026Article
- Circulating tumor DNA-based minimal residual disease-guided adjuvant therapy in solid tumors: Current evidence, clinical trial frameworks, and future directions.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2026Article
- Comparing Real-Time PCR and Amplicon-Based NGS for RoutineDiagnostics (Basel, Switzerland) · 2026Article
- Risk Stratification and Strategies Towards Front-Line Therapy of EGFR-Mutant NSCLC: A Narrative Review.Cancers · 2026Review
- Inhibition of ferroptosis via SLC25A39-NRF2 axis drives Osimertinib resistance in lung adenocarcinoma.Cellular and molecular life sciences : CMLS · 2026Article
- Impact of Variant Allele Frequency (VAF) Levels on Clinical Efficacy of Osimertinib in Patients with Metastatic NSCLC.Medical sciences (Basel, Switzerland) · 2026Review
- Serial Plasma Comprehensive Genomic Profiling Captures Therapy Resistance and Guides Management of Non-Small Cell Lung Cancer.Cancer research communications · 2026Article
- Navigating the landscape of EGFR TKI resistance in EGFR-mutant NSCLC - mechanisms and evolving treatment approaches.Nature reviews. Clinical oncology · 2026Review
- Liquid biopsies for detection, characterization, and interception of therapy resistance in thoracic malignancies.Frontiers in oncology · 2026Review
- Liquid biopsy in cancer drug resistance: real-time monitoring, mechanistic insights, and translational applications.Frontiers in immunology · 2026Review
- Pattern of resistance on first-line EGFR-directed therapy in EGFR-positive metastatic NSCLC.Ecancermedicalscience · 2026Article
- Liquid biopsies across the cancer care continuum.Nature medicine · 2025Review
- Role of signaling pathways in lung cancer development and advances in targeted therapies (Review).Oncology letters · 2025Review
- Review
- Variability of Circulating Tumor DNA Levels in Plasma Samples From Patients With Advanced Non-Small-Cell Lung Cancer in the Absence of Treatment.JCO precision oncology · 2025Article
- Circulating tumor DNA in lung cancer: a bibliometric analysis of studies published from 2001 to 2024.Journal of thoracic disease · 2025Article
- Longitudinal Circulating Tumor DNA-Guided Resistance Analysis During Second-Line Osimertinib Treatment.JTO clinical and research reports · 2025Article
- Cyst fluid ctDNA as a biomarker for genetic profiling and treatment monitoring in cystic brain metastases.British journal of cancer · 2025Article
- Resistance mutations and the blood-brain barrier: Key challenges in targeted treatment of brain metastatic non-small cell lung cancer.Acta pharmaceutica Sinica. B · 2025Review
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Authors and funding
22 authors at 19 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe APPLE trial aimed to evaluate the feasibility of longitudinal plasma epidermal growth factor receptor (EGFR) T790M monitoring for the best sequencing strategy of gefitinib and osimertinib.
methodsAPPLE is a randomized, non-comparative, phase II study in patients with common EGFR-mutant, treatment-naive non-small-cell lung cancer including three arms: arm A (osimertinib upfront until RECIST progression, PD), arm B [gefitinib until emergence of circulating tumor DNA (ctDNA) EGFR T790M mutation by cobas EGFR test v2 or RECIST PD], and arm C (gefitinib until RECIST PD), and then switch to osimertinib in both arms. The primary endpoint is the progression-free survival (PFS) rate 'on osimertinib' at 18 months (PFSR-OSI-18) after randomization in arm B (H
resultsFrom November 2017 to February 2020, 52 and 51 patients were randomized into arms B and C, respectively. Most patients were females (70%) and had EGFR Del19 (65%); one-third had baseline brain metastases. In arm B, 17% of patients (8/47) switched to osimertinib based on the emergence of ctDNA T790M mutation before RECIST PD, with a median time to molecular PD of 266 days. The study met its primary endpoint of PFSR-OSI-18 of 67.2% (84% confidence interval 56.4% to 75.9%) in arm B versus 53.5% (84% confidence interval 42.3% to 63.5%) in arm C, with a median PFS of 22.0 months versus 20.2 months, respectively. The median OS was not reached in arm B versus 42.8 months in arm C. Median brain PFS in arms B and C was 24.4 and 21.4 months, respectively.
conclusionsThe serial monitoring of ctDNA T790M status in advanced EGFR-mutant non-small-cell lung cancer during treatment with first-generation EGFR inhibitors was feasible, and a molecular progression before RECIST PD led to an earlier switch to osimertinib in 17% of patients with satisfactory PFS and OS outcomes.
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