Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Mar 7;16(6):1079.
doi: 10.3390/cancers16061079.

A Real-World Study of Patient Characteristics and Clinical Outcomes in EGFR Mutated Lung Cancer Treated with First-Line Osimertinib: Expanding the FLAURA Trial Results into Routine Clinical Practice

Hollis Viray  1 , Andrew J Piper-Vallillo  1   2 , Page Widick  1 , Emmeline Academia  1 , Meghan Shea  1 , Deepa Rangachari  1 , Paul A VanderLaan  3 , Susumu S Kobayashi  1 , Daniel B Costa  1
Affiliations

A Real-World Study of Patient Characteristics and Clinical Outcomes in EGFR Mutated Lung Cancer Treated with First-Line Osimertinib: Expanding the FLAURA Trial Results into Routine Clinical Practice

Hollis Viray et al. Cancers (Basel). .

Abstract

Osimertinib is a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) that is used for first-line therapy in EGFR mutated non-small cell lung cancer (NSCLC) based on the results of the randomized FLAURA trial (ClinicalTrials.gov number NCT02296125). We performed a retrospective analysis of baseline characteristics and clinical outcomes in 56 real-world patients treated with osimertinib. In total, 45% of patients were determined to be FLAURA-eligible and 55% were FLAURA-ineligible based on the published inclusion/exclusion criteria of the aforementioned trial. For clinical outcomes, the median osimertinib time to treatment discontinuation (TTD) for all patients was 16.9 months (95% CI: 12.6-35.1), whereas the median TTD was 31.1 months (95% CI: 14.9-not reached) in the FLAURA-eligible cohort and the median TTD was 12.2 months (95% CI: 8.1-34.6 months) in the FLAURA-ineligible cohort. Re-biopsy at acquired resistance disclosed both on- and off-target mechanisms. The most common therapies following osimertinib included local therapies followed by post-progression osimertinib, platinum-doublet chemotherapy with or without osimertinib, and osimertinib combinatory targeted therapies. The median overall survival for all patients was 32.0 months (95% CI: 15.7-not reached), the median survival was not reached for the FLAURA-eligible cohort, and it was 16.5 months for the FLAURA-ineligible cohort. Our data support the use of osimertinib in real-word settings and highlight the need for designing registration trials that are more inclusive of patient/disease characteristics seen in routine clinical practice. It is yet to be determined if the use of evolving first-line EGFR inhibitor combination strategies (either platinum-doublet chemotherapy plus osimertinib or amivantamab plus lazertinib) will similarly translate from clinical trials to real-word settings.

Keywords: EGFR; lung cancer; osimertinib; real-world; survival; time to treatment discontinuation.

PubMed Disclaimer

Conflict of interest statement

H.V., A.J.P.-V., P.W., E.A., and M.S. have no conflicts to report. D.R. reports receiving personal fees (consulting fees and honoraria) from TelaDoc Health, DynaMed, and AstraZeneca and nonfinancial support (institutional research support) from Bristol-Myers Squibb, Novocure, and Abbvie/Stemcentrx, all outside the submitted work. P.A.V. reports personal fees (consulting fees) from Gala Therapeutics, Galvanize Therapeutics, Intuitive Surgical, Ruby Robotics, Agilent, and Veracyte, all outside the submitted work. S.S.K. reports research support from Boehringer Ingelheim, MiRXES, Johnson&Johnson, and Taiho Therapeutics, as well as personal fees (honoraria) from AstraZeneca, Boehringer Ingelheim, Bristol Meyers Squibb, Chugai Pharmaceutical, and Takeda Pharmaceuticals, plus royalties from Life Technologies. D.B.C. reports receiving consulting fees and honoraria from Takeda/Millennium Pharmaceuticals, AstraZeneca, Pfizer, Blueprint Medicines, and Janssen, institutional research support from Takeda/Millennium Pharmaceuticals, AstraZeneca, Pfizer, Merck Sharp and Dohme, Merrimack Pharmaceuticals, Bristol Myers Squibb, Clovis Oncology, Spectrum Pharmaceuticals, Tesaro, and Daiichi Sankyo, consulting fees from Teladoc and Grand Rounds by Included Health, and royalties from Life Technologies, all outside the submitted work. No other conflict of interest is reported. The funding sources of the study had no role in the design of the study; in the collection, analyses, or interpretation of the data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Diagram of Beth Israel Deaconess Medical Center (BIDMC) Real-world Cohort with Allocation to FLAURA Clinical Trial Eligibility. Identification of cases to be included in a detailed retrospective medical chart review based on the tumor EGFR mutation status and the use of first-line osimertinib, with designations of FLAURA clinical trial eligibility within the real-world BIDMC cohort. Patients were determined to be FLAURA-ineligible if they either did not meet all FLAURA inclusion criteria or they met a protocol-specified FLAURA exclusion criterion (as per references [8,9]).
Figure 2
Figure 2
Real-World Cohort Clinical Outcomes. (A) Time to treatment discontinuation (TTD) of osimertinib-treated cases in the BIDMC real-world cohort. (B) Overall survival (OS) from the start of osimertinib in BIDMC’s real-world cohort.
Figure 3
Figure 3
Real-World Cohort Clinical Outcomes Stratified by FLAURA Trial Eligibility. (A) Time to treatment discontinuation (TTD) of osimertinib-treated cases in the BIDMC real-world cohort. (B) Overall survival (OS) from the start of osimertinib in BIDMC’s real-world cohort. TTD and OS were stratified by FLAURA-eligible and FLAURA-ineligible status allocation. NR, not reached.
Figure 4
Figure 4
Real-World Cohort Swimmers’ Plots of Osimertib Time to Treatment Discontinuation. (A) Individual case time to treatment discontinuation (TTD) of osimertinib-treated cases in the BIDMC real-world cohort for the FLAURA-eligible cohort. (B) Individual case TTD of osimertinib-treated cases in the BIDMC real-world cohort for the FLAURA-ineligible cohort. The type of EGFR mutation is identified for each case, with “del19” representing EGFR-exon 19 deletions or EGFR-exon 19 indels. The dark blue-filled bars indicate cases that had disease control from osimertinib, while the red-filled bars indicate cases that had primary disease progression on osimertinib, early death while receiving osimertinib, or a lack of assessment of disease control within the initial 6 weeks of osimeritnib prior to discontinuation (additional details in Table 3). The white + symbol indicates cases that continued on the initial osimertinib at the time of data cut-off (i.e., ongoing first-line osimertinib therapy).
See this image and copyright information in PMC

References

    1. Kumar A., Petri E.T., Halmos B., Boggon T.J. Structure and clinical relevance of the epidermal growth factor receptor in human cancer. J. Clin. Oncol. 2008;26:1742–1751. doi: 10.1200/JCO.2007.12.1178. - DOI - PMC - PubMed
    1. Yasuda H., Kobayashi S., Costa D.B. EGFR Exon 20 Insertion Mutations in Non-Small-Cell Lung Cancer: Preclinical Data and Clinical Implications. Lancet Oncol. 2012;13:e23–e31. doi: 10.1016/S1470-2045(11)70129-2. - DOI - PubMed
    1. Sentana-Lledo D., Academia E., Viray H., Rangachari D., Kobayashi S.S., VanderLaan P.A., Costa D.B. EGFR Exon 20 Insertion Mutations and ERBB2 Mutations in Lung Cancer: A Narrative Review on Approved Targeted Therapies from Oral Kinase Inhibitors to Antibody-Drug Conjugates. Transl. Lung Cancer Res. 2023;12:1590–1610. doi: 10.21037/tlcr-23-98. - DOI - PMC - PubMed
    1. Le X., Nadler E., Costa D.B., Heymach J.V. EGFR Tyrosine Kinase Inhibitors for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Uncommon EGFR Mutations: A Podcast. Target. Oncol. 2023;18:807–817. doi: 10.1007/s11523-023-00994-2. - DOI - PMC - PubMed
    1. Sehgal K., Rangachari D., VanderLaan P.A., Kobayashi S.S., Costa D.B. Clinical Benefit of Tyrosine Kinase Inhibitors in Advanced Lung Cancer with EGFR-G719A and Other Uncommon EGFR Mutations. Oncologist. 2021;26:281–287. doi: 10.1002/onco.13537. - DOI - PMC - PubMed

Associated data