Dataset Information

Comparison of clinical outcomes of osimertinib and first-generation EGFR-tyrosine kinase inhibitors (TKIs) in TKI-untreated EGFR-mutated non-small-cell lung cancer with leptomeningeal metastases.

ABSTRACT:

Background

Leptomeningeal metastases (LM) are devastating complications of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). Although osimertinib, a third-generation EGFR-tyrosine kinase inhibitor (TKI), has better penetration into the central nervous system than first-generation EGFR-TKIs, data on the distinct activity of EGFR-TKIs in untreated advanced EGFR-mutated NSCLC with LM are lacking.

Patients and methods

We retrospectively reviewed patients treated with EGFR-TKIs for TKI-untreated common EGFR-mutated NSCLC with LM between July 2002 and July 2021 at the National Cancer Center Hospital. The patients were divided into two groups: patients treated with osimertinib (Osi group) and those treated with gefitinib or erlotinib [first-generation (1G)-TKI group].

Results

Of the 967 patients, 71 were eligible, including 29 in the Osi group and 42 in the 1G-TKI group. The median progression-free survival (PFS) and overall survival (OS) in the Osi group were better than those in the 1G-TKI group (PFS: 16.9 months versus 8.6 months, P = 0.007, and OS: 26.6 months versus 20.0 months, P = 0.158). The LM-overall response rate (ORR) and LM-PFS were significantly better in the Osi group than in the 1G-TKI group (LM-ORR: 62.5% versus 25.7%, P = 0.007; LM-PFS: 23.4 months versus 12.1 months, P = 0.021). In the subgroup analysis of EGFR mutation status, LM-PFS for patients with exon 19 deletion was significantly longer in the Osi group than in the 1G-TKI group (32.7 months versus 13.4 months, P = 0.013), whereas those with L858R mutation in exon 21 did not differ between the two groups. In the multivariate analysis, osimertinib and exon 19 deletion were significant factors for better LM-PFS and OS.

Conclusion

Osimertinib can be more effective for untreated common EGFR-mutated NSCLC patients with LM, especially those with exon 19 deletion, compared to first-generation TKIs.

SUBMITTER: Tamura K

PROVIDER: S-EPMC10485398 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Comparison of clinical outcomes of osimertinib and first-generation EGFR-tyrosine kinase inhibitors (TKIs) in TKI-untreated EGFR-mutated non-small-cell lung cancer with leptomeningeal metastases.

Tamura K K Yoshida T T Masuda K K Matsumoto Y Y Shinno Y Y Okuma Y Y Goto Y Y Horinouchi H H Yamamoto N N Ohe Y Y

ESMO open 20230728 4

<h4>Background</h4>Leptomeningeal metastases (LM) are devastating complications of epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). Although osimertinib, a third-generation EGFR-tyrosine kinase inhibitor (TKI), has better penetration into the central nervous system than first-generation EGFR-TKIs, data on the distinct activity of EGFR-TKIs in untreated advanced EGFR-mutated NSCLC with LM are lacking.<h4>Patients and methods</h4>We retrospectively reviewed patie ...[more]

PMID: 37517364

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Project description:BackgroundIn the global FLAURA study, first-line osimertinib, a third-generation irreversible tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), significantly improved progression-free survival (PFS) and overall survival (OS) versus comparator EGFR TKIs in patients with EGFR mutation-positive (EGFRm) advanced non-small-cell lung cancer (NSCLC).ObjectiveThe FLAURA China study assessed first-line osimertinib in Chinese patients with EGFRm advanced NSCLC (NCT02296125).MethodsFLAURA China was a double-blind, randomized, phase III study. Adults from mainland China with previously untreated EGFRm (Exon 19 deletion or L858R) advanced NSCLC were enrolled in the global study or a China-only study under the same protocol; 136 patients were randomized to osimertinib (80 mg once daily [od]; n = 71) or comparator EGFR TKI (gefitinib or erlotinib; all sites selected gefitinib 250 mg od; n = 65). Patients were randomized and allocated to treatment groups by a central computer system. Treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was investigator-assessed PFS; OS was a secondary endpoint.ResultsAll 136 randomized patients were analyzed. Osimertinib extended median PFS by 8.0 months versus comparator EGFR TKI (17.8 vs. 9.8 months; hazard ratio [HR] 0.56; 95% confidence interval [CI] 0.37-0.85). Median OS was 33.1 months in the osimertinib group versus 25.7 months in the comparator group (HR 0.85; 95% CI 0.56-1.29). At 3 years, 20% of patients on osimertinib and 8% on the comparator remained on randomized treatment. Grade 3 or higher adverse events (AEs) were reported in 54 and 28% of patients in the osimertinib and comparator groups, respectively, driven by increased local reporting of laboratory- and disease-related AEs. No new safety signals were identified.ConclusionsFirst-line osimertinib treatment resulted in a clinically meaningful PFS and OS benefit versus comparator EGFR TKI in Chinese patients with EGFRm advanced NSCLC. Safety data were consistent with the known safety profile of osimertinib.Clinical trial registrationClinicalTrials.gov NCT02296125, registered 20 November 2014.

Dataset Information

Comparison of clinical outcomes of osimertinib and first-generation EGFR-tyrosine kinase inhibitors (TKIs) in TKI-untreated EGFR-mutated non-small-cell lung cancer with leptomeningeal metastases.

Background

Patients and methods

Results

Conclusion

Publications

Comparison of clinical outcomes of osimertinib and first-generation EGFR-tyrosine kinase inhibitors (TKIs) in TKI-untreated EGFR-mutated non-small-cell lung cancer with leptomeningeal metastases.

Similar Datasets

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