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Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI

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Abstract

Background

Osimertinib is effective in non-small-cell lung cancer (NSCLC) with an acquired epidermal growth factor receptor (EGFR) T790M mutation, the most common resistance mechanism to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs).

Objectives

We aimed to evaluate survival outcome of patients with EGFR-mutant NSCLC who have progressed on previous EGFR TKI therapy.

Patients and Methods

Advanced NSCLC patients with EGFR mutation after acquired resistance to first- or second-generation EGFR TKI who received tumor rebiopsy after EGFR TKI failure from 1 January 2012 to 31 December 2017 were reviewed. Patient clinical characteristics, T790M mutation status, and post-progression survival (PPS) were recorded by chart review.

Results

We included 240 patients and the percentage of secondary T790M mutations in first time tissue rebiopsy was 52.9%. 38 of the initial T790M-negative patients received second rebiopsies and 14 (36.8%) of these were T790M positive. The duration between first and second rebiopsy tended to be longer in patients who had T790M mutation in the second biopsy (11.5 vs. 6.9 months, p = 0.043). After EGFR TKI failure, the median PPS of patients who had the T790M mutation and history of osimertinib use was 42.6 months (95% CI 34.6–50.5), compared to 18.0 (95% CI 9.6–26.4) months in T790M-positive patients without a history of osimertinib use, and 18.8 (95% CI 9.3–28.4) months in patients with no T790M mutation (p < 0.0001). Multivariate analysis showed that history of osimertinib use was correlated with improved survival.

Conclusions

These data further emphasize that osimertinib should be a standard of care in patients with pretreated EGFR T790M-positive NSCLC.

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Funding

This work was supported by the Ministry of Health and Welfare, Taiwan (MOHW109-TDU-B-211–134019).

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Authors and Affiliations

  1. Department of Chest Medicine, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei, 112, Taiwan

    Chi-Lu Chiang, Hsu-Ching Huang, Chia-I Shen, Yung-Hung Luo, Yuh-Min Chen & Chao-Hua Chiu

  2. Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Chi-Lu Chiang, Hsu-Ching Huang, Yung-Hung Luo, Yuh-Min Chen & Chao-Hua Chiu

  3. Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

    Chi-Lu Chiang & Yung-Hung Luo

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  1. Chi-Lu Chiang
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Contributions

All authors made substantial contributions to the conception and design, or analysis and interpretation of data, and to the drafting of the manuscript or revising it critically for important intellectual content. Additionally, all authors provided final approval of the version to be submitted.

Corresponding author

Correspondence to Chao-Hua Chiu.

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Conflict of interest

C.H.C. and C.L.C. have received honoraria from AstraZeneca, Boehringer Ingelheim, and Roche. H.C.H, C.I.S, Y.H.L, and Y.M.C declared no conflict of interest that might be relevant to the contents of this article.

Ethics approval

The Institutional Review Board of Taipei Veterans General Hospital approved this study (IRB No. 2019–07-031CC).

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Chiang, CL., Huang, HC., Shen, CI. et al. Post-Progression Survival in Secondary EGFR T790M-Mutated Non-Small-Cell Lung Cancer Patients With and Without Osimertinib After Failure of a Previous EGFR TKI. Targ Oncol 15, 503–512 (2020). https://doi.org/10.1007/s11523-020-00737-7

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  • DOI: https://doi.org/10.1007/s11523-020-00737-7

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