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Multicenter Study
. 2024 Oct 20;42(30):3606-3617.
doi: 10.1200/JCO.23.02668. Epub 2024 Jul 24.

Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From EGFR and ALK Oncogene-Driven Non-Small Cell Lung Cancer (TURBO-NSCLC)

Luke R G Pike  1 , Emily Miao  1   2 , Lillian A Boe  3 , Tejas Patil  4 , Brandon S Imber  1 , Nathaniel J Myall  5 , Erqi L Pollom  6 , Caressa Hui  6 , Vera Qu  6 , Jacob Langston  7 , Veronica Chiang  8 , Michael Grant  9 , Sarah B Goldberg  9 , Joshua D Palmer  10 , Rahul N Prasad  10 , Tony J C Wang  11 , Albert Lee  11 , Catherine A Shu  12 , Lanyi Nora Chen  12 , Nicholas J Thomas  13 , Steve E Braunstein  14 , Brian D Kavanagh  7 , D Ross Camidge  4 , Chad G Rusthoven  7
Affiliations
Multicenter Study

Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From EGFR and ALK Oncogene-Driven Non-Small Cell Lung Cancer (TURBO-NSCLC)

Luke R G Pike et al. J Clin Oncol. .

Abstract

Purpose: Newer-generation tyrosine kinase inhibitors (TKIs) for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements have demonstrated high CNS activity. The optimal use of up-front stereotactic radiosurgery (SRS) for brain metastases (BM) in patients eligible for CNS-penetrant TKIs is controversial, and data to guide patient management are limited.

Materials and methods: Data on TKI-naïve patients with EGFR- and ALK-driven NSCLC with BM treated with CNS-penetrant TKIs with and without up-front SRS were retrospectively collected from seven academic centers in the United States. Time-to-CNS progression and overall survival (OS) were analyzed, with multivariable adjustment in Fine & Gray and Cox proportional hazards models for clinically relevant factors.

Results: From 2013 to 2022, 317 patients were identified (200 TKI-only and 117 TKI + SRS). Two hundred fifty (79%) and 61 (19%) patients received osimertinib and alectinib, respectively. Patients receiving TKI + SRS were more likely to have BM ≥1 cm (P < .001) and neurologic symptoms (P < .001) at presentation. Median OS was similar between the TKI and TKI + SRS groups (median 41 v 40 months, respectively; P = .5). On multivariable analysis, TKI + SRS was associated with a significant improvement in time-to-CNS progression (hazard ratio [HR], 0.63 [95% CI, 0.42 to 0.96]; P = .033). Local CNS control was significantly improved with TKI + SRS (HR, 0.30 [95% CI, 0.16 to 0.55]; P < .001), whereas no significant differences were observed in distant CNS control. Subgroup analyses demonstrated a greater benefit from TKI + SRS in patients with BM ≥1 cm in diameter for time-to-CNS progression and CNS progression-free survival.

Conclusion: The addition of up-front SRS to CNS-penetrant TKI improved time-to-CNS progression and local CNS control, but not OS, in patients with BM from EGFR- and ALK-driven NSCLC. Patients with larger BM (≥1 cm) may benefit the most from up-front SRS.

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Conflict of interest statement

Conflicts of Interest:

Luke R.G. Pike reports consulting agreements with Blackstone Investments/Clarus Ventures, Third Rock Ventures, Deerfield Investments, Aviko Inc, Monograph Capital, Genece Health, DxCover, Galera Therapeutics, Dynamo Therapeutics, Myst Therapeutics, Monte Rosa Therapeutics, Best Doctors/Teladoc Inc, Turnstone Biologics; equity and stock ownership of Schrodinger, Novavax, Clovis Oncology; research funding from Delfi Diagnostics, Caris Life Sciences, Harbinger Health, Genece Health, Varian, and the Department of Defense.

Tejas Patil is a consultant/advisory board member for AstraZeneca, Biocept, Boehringer Ingelheim, Bristol-Myers Squibb, Bicara, Caris, Daiichi, Guardant Health, EMD Soreno, Janssen, Jazz Pharamceuticals, Mirati Therapeutics, Natera, Pfizer, Sanofi, Regeneron, Roche/Genentech, Takeda, Elevation Oncology (DSMB) and reports research funding from EMD Soreno, Janssen, and Gilead.

Brandon Imber reports research funding from AstraZeneca, Kazia Therapeutics, GT Medical Technologies, Novartis, Bayer; honoraria from GT Medical Technologies and Telix Pharmaceuticals.

Veronica Chiang is a consultant for Monteris Medical Inc and a speaker for BrainLab AG.

Sarah Goldberg reports research funding from AstraZeneca, Boehringer Ingelheim, Mirati and is a consultant/advisory board member for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, Amgen, Blueprint Medicine, Sanofi Genzyme, Daiichi-Sankyo, Takeda, Janssen, Summit Therapeutics, Merck and Regeneron.

Joshua D. Palmer reports research funding from Genentech; honoraria from Varian Medical Systems, Novocure, ICOTEC, Carbofix.

Tony J. C. Wang reports personal fees and nonfinancial support from AbbVie; personal fees from Cancer Panels, Doximity, Elekta, and Novocure Wolters Kluwer, Iylon Precision Oncology; nonfinancial support from Merck; grants and nonfinancial support from RTOG Foundation, Genentech, and Varian.

Catherine A. Shu is a consultant/advisory board member for AstraZeneca, Genentech, Janssen, Takeda, Gilead, and reports personal fees from Mirati.

Steve Braunstein reports grant funding from Merck, Elekta; payment/honoraria from RadOnc Questions, LLC; and consulting fees Novocure, and Icotec.

D. Ross Camidge reports consulting fees from AstraZeneca and Roche.

All other authors declare that they have no conflicts of interest.

References

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