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

Remón, Jordi; Besse, Benjamin; Aix, Santiago Ponce; Callejo, Ángel; Al-Rabi, K.; Bernabé, R.; Greillier, L.; Majem, Margarita; Reguart, Noemı́; Monnet, Isabelle; Cousin, S.; Garrido, Pilar; Robinet, G.; Campelo, Rosario García; Madroszyk, Anne; Curcio, H.; Wasąg, Bartosz; Pretzenbacher, Y.; Fournier, B.; Dingemans, A-M. C.; Dziadziuszko, Rafał

doi:10.1016/j.annonc.2023.02.012

Cited by 35 publications

(18 citation statements)

References 26 publications

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“…The APPLE trial previously met its primary end point of PFS on osimertinib at 18 months in a sequential arm . 1 In the current updated analysis, prospective assessment of secondary end points demonstrates that up-front treatment with osimertinib shows a clinically meaningful lower rate of brain progression versus sequential treatment approach, consistent with osimertinib features and not explored clinically so far. However, comparable OS was observed between both treatment strategies.…”

Section: Discussionmentioning

confidence: 66%

“…Secondary end points included PFS, the overall survival (OS), and the brain PFS (BPFS). 1 Radiologic tumor assessment by body contrasted-enhanced computed tomography scan was performed every 8 weeks independent of delayed or interrupted doses.…”

Section: Introductionmentioning

confidence: 99%

“…The trial met its primary end point of PFSR-OSI-18 by 67.2% (84% CI, 56.4 to 75.9) in arm B versus 53.5% (84% CI, 42.3 to 63.5) in arm C, with a median PFS of 22.0 months versus 20.2 months, respectively. 1 Here, we present the final OS of the trial and the exploratory analysis of the outcome with osimertinib up front versus the sequential approach. Therefore, arms B and C have been pooled for the present analyses.…”

Section: Introductionmentioning

confidence: 99%

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Overall Survival From the EORTC LCG-1613 APPLE Trial of Osimertinib Versus Gefitinib Followed by Osimertinib in Advanced EGFR-Mutant Non–Small-Cell Lung Cancer

Remon,

Besse,

Aix

et al. 2024

JCO

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Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Osimertinib has been established as a standard of care for patients with common sensitizing EGFR-mutant advanced non–small-cell lung cancer (NSCLC) although the sequential approach (first-generation inhibitor gefitinib followed by osimertinib) has not been formally compared. The phase II APPLE trial (ClinicalTrials.gov identifier: NCT02856893 ) enrolled 156 treatment-naïve patients, and two treatment strategies were evaluated: osimertinib up front or the sequential treatment approach with gefitinib up front followed by osimertinib at the time of progression, either molecular progression (detection of plasma T790M resistance mutation) regardless of the radiologic status or just at the time of radiologic progression. Patients' characteristics were well balanced, except for the higher proportion of baseline brain metastases in the sequential approach (29% v 19%). Per protocol, 73% of patients switched to osimertinib in the sequential arm. Up-front treatment with osimertinib was associated with a lower risk of brain progression versus the sequential approach (hazard ratio [HR], 0.54 [90% CI, 0.34 to 0.86]), but a comparable overall survival was observed between both strategies (HR, 1.01 [90% CI, 0.61 to 1.68]), with the 18-month survival probability of 84% and 82.3%, respectively. The APPLE trial suggests that a sequential treatment approach is associated with more frequent progression in the brain but a similar survival in advanced EGFR-mutant NSCLC.

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Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Overall Survival From the EORTC LCG-1613 APPLE Trial of Osimertinib Versus Gefitinib Followed by Osimertinib in Advanced EGFR-Mutant Non–Small-Cell Lung Cancer

Remon,

Besse,

Aix

et al. 2024

JCO

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“…In summary, we studied and analyzed the clinical and pathological features of lung adenocarcinoma patients with only EGFR-T790M primary mutation, and discussed its possible physiological mechanism, to provide objective evidences for clinical treatment of this kind of disease. As other scholars have put forward in studying the carcinogenic drivers of NSCLC, many data of clinical treatment of NSCLC support that the survival bene t of patients with NSCLC may mainly be to formulate personalized schemes for precise treatment, rather than simply delaying the progress of the disease through more effective medicines used in the early stage [45][46][47] . Undeniably, the sample of LUAD cases with only EGFR-T790M primary mutation in our article is relatively small, and other factors of patients themselves may affect the characteristics and physiological mechanism of LUAD with only EGFR-T790M primary mutation, so a larger sample is needed to prove it.…”

Section: Discussionmentioning

confidence: 99%

The clinicopathological features and possible physiological mechanisms of only EGFR-T790M primary mutation in lung adenocarcinoma patients

zhao,

Xu,

Zhu

et al. 2024

Preprint

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The EGFR-T790M mutation often increases the difficulty of treatment in non-small cell lung cancer patients. The only EGFR-T790M primary mutation of the lung adenocarcinoma(LUAD) is rare, there are relatively few reports on the clinicopathological characteristics and physiological mechanisms of this disease. We collected the clinical data of LUAD patients with only EGFR-T790M primary mutation to analyze the Clinicopathological features and possible physiological mechanism and provide evidences for clinical treatment. We found that the β-Catenin and Cyclin D1 were strongly positive. Only using the EGFR TKIs to treat this disease can obtain a partial response(PR) time of less than 8 months, Serum CYFRA 21 − 1 was significantly increased in the patient with Ki67 and mutant P53 positive, and the tumor cells are easy to metastasize and have a fast course of disease. The patient with negative Ki67 and mutant P53 underwent surgical resection and adjuvant chemotherapy, and the progression-free survival (PFS) time was 25 months. Our findings reveal that only EGFR-T790M primary mutation has no concern with the staging of lung cancer, it is related to the abnormal activation of Wnt signaling pathway; The combination of Ki67 and mutated P53 may be used as a prognostic indicator for this kind of patients.

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“…In preclinical models and initial clinical trials, the hindrance of EGFR exhibited potent antitumor properties. [9][10][11] However, certain clinical investigations have revealed that gefitinib does not lead to prostate-specific antigen (PSA) or objectively measurable CRPC responses. [12][13][14] In the meantime, the coadministration of GEF alongside other medications failed to manifest notable antitumor efficacy in PCa.…”

Section: Introductionmentioning

confidence: 99%

Delivery of gefitinib loaded nanoparticles for effectively inhibiting prostate cancer progression

Xiong,

Tong,

Xie

et al. 2024

Biomater. Sci.

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show abstract

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

Cited by 35 publications

References 26 publications

Overall Survival From the EORTC LCG-1613 APPLE Trial of Osimertinib Versus Gefitinib Followed by Osimertinib in Advanced EGFR-Mutant Non–Small-Cell Lung Cancer

Overall Survival From the EORTC LCG-1613 APPLE Trial of Osimertinib Versus Gefitinib Followed by Osimertinib in Advanced EGFR-Mutant Non–Small-Cell Lung Cancer

The clinicopathological features and possible physiological mechanisms of only EGFR-T790M primary mutation in lung adenocarcinoma patients

Delivery of gefitinib loaded nanoparticles for effectively inhibiting prostate cancer progression

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