Overall survival in advanced epidermal growth factor receptor mutated non-small cell lung cancer using different tyrosine kinase inhibitors in The Netherlands: a retrospective, nationwide registry study

Gijtenbeek, Rolof G.P.; Damhuis, Ronald A.; Wekken, Anthonie J. van der; Hendriks, Lizza; Groen, Harry J.M.; Geffen, Wouter H. van

doi:10.1016/j.lanepe.2023.100592

Cited by 24 publications

(21 citation statements)

References 46 publications

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“…This observation has also been reported in the setting of real-world data. 5 Similarly, the comparable OS data in the APPLE trial cannot be explained by an overselected population in arm B/C pooled as patients in this arm had a higher proportion of baseline brain metastases versus the osimertinib up-front arm. Indeed, in the sequential arm, 75% of patients (50 of 66) switched to osimertinib only on the basis of RECIST PD.…”

Section: Discussionmentioning

confidence: 97%

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: 97%

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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“…• Stereotactic radiation/γknife therapy for brain metastasis Passage of one or more days from the final irradiation day (final irradiation day on the registration day will not be accepted). 13. Obtainment of written consent from the patient himself/herself after sufficient explanation of the study content before registration in this study.…”

Section: Sample Sizementioning

confidence: 99%

“…3 These discrepancies in the treatment outcomes of osimertinib by EGFR mutation subtype are also apparent in real-world data from patients with advanced treatment-naïve EGFR mutation-positive NSCLC who were administered osimertinib. [11][12][13] In contrast, the RELAY study showed that the PFS extending the effect of combination therapy exhibited a similar trend in patients with exon 19 deletion [HR, 0.65 (95% CI: 0.47-0.90)] and L858R mutation [HR, 0.62 (95% CI: 0.44-0.87)]. 4 These results suggest that combination therapy with erlotinib plus ramucirumab may be superior to osimertinib monotherapy in L858R mutation-positive patients, and a phase III clinical trial for this population is currently underway.…”

Section: Introductionmentioning

confidence: 99%

Rationale and design of phase II clinical trial of dual inhibition with ramucirumab and erlotinib in EGFR exon 19 deletion-positive treatment-naïve non-small cell lung cancer with high PD-L1 expression (SPIRAL-3D study)

et al. 2023

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Background: Osimertinib is a standard treatment option for epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). However, osimertinib monotherapy yields poor clinical outcomes in some patients, necessitating the development of novel treatment strategies. In addition, several studies have suggested that high programmed cell death-ligand 1 (PD-L1) expression is associated with poor progression-free survival (PFS) for osimertinib monotherapy in patients with advanced NSCLC harboring EGFR mutations. Objective: To evaluate the clinical efficacy of erlotinib plus ramucirumab for EGFR exon 19 deletion-positive treatment-naïve NSCLC with high PD-L1 expression. Design: A single-arm, prospective, open-label, phase II study Methods and Analysis: Patients with treatment-naïve EGFR exon 19 deletion-positive NSCLC with high PD-L1 expression and a performance status of 0–2 will receive combination therapy with erlotinib plus ramucirumab until evidence of disease progression or development of unacceptable toxicity. High PD-L1 expression is defined as a tumor proportion score of 50% or higher, as determined by PD-L1 immunohistochemistry 22C3 pharmDx testing. The Kaplan–Meier method and the Brookmeyer and Crowley method with the arcsine square-root transformation will be used with PFS as the primary endpoint. The secondary endpoints include overall response rate, disease control rate, overall survival, and safety. A total of 25 patients will be enrolled. Ethics: The study has been approved by the Clinical Research Review Board, Kyoto Prefectural University of Medicine, Kyoto, Japan, and written informed consent will be obtained from all patients. Discussion: To the best of our knowledge, this is the first clinical trial to focus on PD-L1 expression in EGFR mutation-positive NSCLC. If the primary end point is met, combination therapy with erlotinib and ramucirumab could become a potential treatment option for this clinical population. Trial Registration: This trial was registered with the Japan Registry for Clinical Trials on 12 January 2023 (jRCTs 051220149).

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“…Previous studies have reported several sensitive mutations among the uncommon mutations in EGFR, including G719X, S768I, and L861Q, which have preliminarily shown responsiveness to both afatinib and osimertinib, with better brain infiltration in NSCLC patients 6,8 . Compared with the second‐generation TKIs, the efficacy of the first‐generation TKIs not manifested the surprising results 10–13 . Later, afatinib had been approved by U.S. Food and Drug Administration as the standard therapy regimen for NSCLC patients with metastasis and uncommon mutations, including G719X, S768I, and L861Q, for which the efficacy and benefit of second‐ and third‐TKIs have been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

Comparison of efficacy and safety of second‐ and third‐generationTKIsfor non‐small‐cell lung cancer with uncommonEGFRmutations

Hao

Jin

et al. 2023

Cancer Medicine

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BackgroundThe efficacy of definite for non‐small‐cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR) mutations has been preliminarily demonstrated. However, there is a paucity of data with which to compare the efficacy and safety of second‐ and third‐generation TKIs in patients with NSCLC carrying uncommon EGFR mutations.MethodsWe compared the efficacy and safety of second‐ and third‐generation TKIs in all NSCLC patients in whom next‐generation sequencing confirmed uncommon EGFR mutations, including G719X, S768I, and L861Q. The parameters analyzed included the objective response rate (ORR), disease control rate (DCR), progression‐free survival (PFS), and overall survival (OS). The rate of treatment‐related adverse events (AEs) reflected the safety of these TKIs.ResultsEighty‐four NSCLC patients with uncommon EGFR mutations were enrolled between April 2016 and May 2022 at Zhejiang Cancer Hospital, including 63 treated with second‐generation TKIs and 21 treated with third‐generation TKIs. The ORR for all patients receiving TKIs was 47.6%, and the DCR was 86.9%. The median PFS for NSCLC patients with uncommon EGFR mutations receiving TKIs was 11.9 months and OS was 30.6 months. There was no significant difference in PFS after treatment with second‐ or third‐generation TKIs (13.3 vs. 11.0 months, respectively, P = 0.910) or in OS (30.6 vs. 24.6 months, respectively P = 0.623). The third‐generation TKIs showed no severe toxicity.ConclusionsThe efficacy of second‐ and third‐generation TKIs for NSCLC with uncommon EGFR mutations does not differ, and so can be used to treat NSCLC patients with these mutations.

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Overall survival in advanced epidermal growth factor receptor mutated non-small cell lung cancer using different tyrosine kinase inhibitors in The Netherlands: a retrospective, nationwide registry study

Cited by 24 publications

References 46 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

Rationale and design of phase II clinical trial of dual inhibition with ramucirumab and erlotinib in EGFR exon 19 deletion-positive treatment-naïve non-small cell lung cancer with high PD-L1 expression (SPIRAL-3D study)

Comparison of efficacy and safety of second‐ and third‐generationTKIsfor non‐small‐cell lung cancer with uncommonEGFRmutations

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