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) Journal Article
| Authors: | Pike, L. R. G.; Miao, E.; Boe, L. A.; Patil, T.; Imber, B. S.; Myall, N. J.; Pollom, E. L.; Hui, C.; Qu, V.; Langston, J.; Chiang, V.; Grant, M.; Goldberg, S. B.; Palmer, J. D.; Prasad, R. N.; Wang, T. J. C.; Lee, A.; Shu, C. A.; Chen, L. N.; Thomas, N. J.; Braunstein, S. E.; Kavanagh, B. D.; Camidge, D. R.; Rusthoven, C. G. |
| Article Title: | 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) |
| 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 METHODSData 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. © 2024 American Society of Clinical Oncology. |
| Keywords: | adult; aged; aged, 80 and over; middle aged; retrospective studies; genetics; mutation; clinical trial; brain tumor; brain neoplasms; protein kinase inhibitor; carcinoma, non-small-cell lung; lung neoplasms; epidermal growth factor receptor; pathology; pyrimidines; retrospective study; tyrosine kinase inhibitors; protein tyrosine kinase inhibitor; protein kinase inhibitors; lung tumor; multicenter study; radiosurgery; piperidines; aniline compounds; drug therapy; indoles; pyrimidine derivative; indole derivative; egfr protein, human; carbazoles; non small cell lung cancer; anaplastic lymphoma kinase; piperidine derivative; acrylamides; aniline derivative; carbazole derivative; erbb receptors; very elderly; humans; human; male; female; acrylamide derivative; alectinib; osimertinib; alk protein, human |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 42 |
| Issue: | 30 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2024-10-20 |
| Start Page: | 3606 |
| End Page: | 3617 |
| Language: | English |
| DOI: | 10.1200/jco.23.02668 |
| PUBMED: | 39047224 |
| PROVIDER: | scopus |
| PMCID: | PMC11874932 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus |
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