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Local control of brain metastases with osimertinib alone in patients with EGFR-mutant non-small cell lung cancer

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Abstract

Purpose

Although osimertinib has excellent intracranial activity in metastatic non-small cell lung cancer (NSCLC) with exon 19 deletion or L858R EGFR alterations, measures of local control of brain metastases are less well-reported. We describe lesion-level outcomes of brain metastases treated with osimertinib alone.

Methods

We retrospectively reviewed patients with EGFR-mutant NSCLC with untreated brain metastasis measuring ≥ 5 mm at the time of initiating osimertinib. Cumulative incidence of local recurrence in brain (LRiB) was calculated with death as a competing risk, and univariable and multivariable analyses were conducted to identify factors associated with LRiB.

Results

We included 284 brain metastases from 37 patients. Median follow-up was 20.1 months. On initial MRI after starting osimertinib, patient-level response was complete response (CR) in 11 (15%), partial response (PR) in 33 (45%), stable disease (SD) in 18 (25%) and progressive disease (PD) in 11 (15%). The 1-year cumulative incidence of LRiB was 14% (95% CI 9.9–17.9) and was significantly different in patients with a CR (0%), PR (4%), and SD (11%; p = 0.02). Uncontrolled primary tumor (adjusted hazard ratio [aHR] 3.78, 95% CI 1.87–7.66; p < 0.001), increasing number of prior systemic therapies (aHR 2.12, 95% CI 1.49–3.04; p < 0.001), and higher ECOG score (aHR 7.8, 95% CI 1.99–31.81; p = 0.003) were associated with LRiB.

Conclusions

Although 1-year cumulative incidence of LRiB is < 4% with a CR or PR, 1-year cumulative incidence of LRiB is over 10% for patients with less than a PR to osimertinib on initial MRI. These patients should be followed closely for need for additional treatment such as stereotactic radiosurgery.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

Authors

Contributions

CH: Conceptualization, Methodology, Validation, Investigation, Data Curation, Writing—Original Draft, Writing—Review & Editing, Visualization, Project administration. VQ: Investigation, Data Curation, Writing—Original Draft, Writing—Review & Editing. J-YW: Investigation, Writing—Review & Editing. RvE: Formal Analysis, Writing—Review & Editing. Y-CC, P-LC, C-HL, J-TL: Formal Analysis, Resources, Writing—Review & Editing. GL, MH-G, HW, JN, KR, MD, SN: Writing—Review & Editing, Visualization. SS: Conceptualization, Methodology, Writing—Original Draft, Writing—Review & Editing. NM: Conceptualization, Methodology, Validation, Writing – Original Draft, Writing—Review & Editing, Supervision, Project administration. EP: Conceptualization, Methodology, Validation, Data Curation, Writing—Original Draft, Writing—Review & Editing, Supervision, Project administration.

Corresponding authors

Correspondence to Nathaniel Myall or Erqi Pollom.

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Conflict of interest

For authors Yu-Cheng Chang, Po-Lin Chiang, Chih-Hung Liang, Jen-Tang Lu, a US patent is granted for Vysioneer software, and these authors also have Vysioneer Inc. stocks. For author Scott Soltys: Zap Surgical, Inc.—Speaker Honoraria; Novocure, Inc.—Research Funding; Accuray, Inc.—Consultant. For author Millie Das: Consulting: Jazz Pharmaceutics, Beigene, Astra Zeneca, Sanofi/Genzyme, Eurofins, Janssen, Genentech (uncompensated). Research: Merck, Genentech, CellSight, Novartis, Abbvie, United Therapeutics, Varian, Verily, Celgene. For author Melanie Hayden-Gephart: U54CA261717. All other authors have no conflicts of interest.

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Hui, C., Qu, V., Wang, JY. et al. Local control of brain metastases with osimertinib alone in patients with EGFR-mutant non-small cell lung cancer. J Neurooncol 160, 233–240 (2022). https://doi.org/10.1007/s11060-022-04145-x

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