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)

Author(s): Luke R.G. Pike, MD, DPhil¹; Emily Miao, PharmD^1,2; Lillian A. Boe, PhD³; Tejas Patil, MD⁴; Brandon S. Imber, MD¹; Nathaniel J. Myall, MD⁵; Erqi L. Pollom, MD, MS⁶; Caressa Hui⁶; Vera Qu, MD⁶; Jacob Langston, MD⁷; Veronica Chiang, MD⁸; Michael Grant, MD⁹; Sarah B. Goldberg, MD, MPH⁹; Joshua D. Palmer, MD¹⁰; Rahul N. Prasad, MD, MBA¹⁰; Tony J.C. Wang, MD¹¹; Albert Lee, MD¹¹; Catherine A. Shu, MD¹²; Lanyi Nora Chen, MD¹²; Nicholas J. Thomas, MD¹³; Steve E. Braunstein, MD, PhD¹⁴; Brian D. Kavanagh, MD⁷; D. Ross Camidge, MD, PhD⁴; Chad G. Rusthoven, MDedu⁷

Source: https://doi.org/10.1200/JCO.23.02668

Dr. Maen Hussein's Thoughts

Adding SBRT improves local control and disease progression in the brain but not overall survival. Do the radiation oncologists have input? Is it worth it to control symptoms?

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.

Author Affiliations

¹Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY; ²Albert Einstein College of Medicine, Bronx, NY; ³Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY; ⁴Division of Hematology and Oncology, Department of Medicine, University of Colorado, Aurora, CO; ⁵Division of Hematology and Oncology, Department of Medicine, Stanford University, Palo Alto, CA; ⁶Department of Radiation Oncology, Stanford University, Palo Alto, CA; ⁷Department of Radiation Oncology, University of Colorado, Aurora, CO; ⁸Department of Neurosurgery, Yale University, New Haven, CT; ⁹Division of Medical Oncology, Department of Medicine, Yale School of Medicine, New Haven, CT; ¹⁰Department of Radiation Oncology, Ohio State University, Columbus, OH; ¹¹Department of Radiation Oncology, Columbia University Irving Medical Center, New York, NY; ¹²Division of Hematology and Oncology, Department of Medicine, Columbia University Irving Medical Center, New York, NY; ¹³Department of Medicine, University of California San Francisco, San Francisco, CA; ¹⁴Department of Radiation Oncology, University of California San Francisco, San Francisco, CA

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