Upfront SRS Recommended For TKI-Naïve EGFR-mutated NSCLC Brain Metastases

Stereotactic surgery suggested first-line therapy for epidermal growth factor receptor-mutated non-small-cell cancer patients with brain metastases who are naïve to tyrosine kinase inhibitor therapy

medwireNews: Stereotactic surgery (SRS) followed by epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy may be the optimal regimen for non-small-cell lung cancer (NSCLC) patients with brain metastases who have not previously received treatment targeted at a EGFR mutation, a review suggests.

The analysis published in the Journal of Clinical Oncology examined the outcomes of 351 EGFR–TKI-naïve patients treated at one of six institutions in the USA between 2008 and 2014 for newly diagnosed brain metastases and followed-up for a median of 22 months.

Median overall survival (OS) for the 100 patients given SRS followed by EGFR–TKI therapy was 46 months, report Veronica Chiang, from Yale School of Medicine in New Haven, Connecticut, USA, and co-authors.

This was significantly longer than the 30 months achieved by the 120 patients given whole-brain radiotherapy (WBRT) followed by EGFR–TKI therapy and the 25 months reported for the 131 patients whose initial treatment was EGFR–TKI therapy followed by SRS or WBT on intracranial progression.

Two-year OS was achieved by 78%, 62% and 51% of the upfront SRS, WBRT and EGFR–TKI therapy groups, respectively.

Multivariate analysis confirmed that upfront use of SRS or WBT versus EGFR–TKI therapy were significant predictors of better OS, with hazard ratios (HRs) of 0.39 and 0.70, respectively.

Other positive predictive factors included younger patient age and better performance status, the presence of the EGFR exon 19 mutation versus the exon 20 or 21 variants, and absence of extracranial metastases.

Further analysis showed that the median time to intracranial progression was significantly longer with upfront SRS or WBRT than EGFR–TKI therapy (23 and 24 vs 17 months, respectively).

When patients were classified by the disease-specific Graded Prognostic Assessment, those with a favourable prognosis who received upfront SRS had significantly longer median OS than those treated with upfront WBRT or EGFR-TKI therapy (64 vs 52 and 32 months, respectively). And a similar pattern was also found for patients with a less favourable prognosis (33 vs 27 and 19 months).

In all, 76% of patients experienced disease progression; analysis failed to find a significant correlation between OS and receipt of subsequent therapies, such as carboplatin or cisplatin plus pemetrexed.

“SRS followed by EGFR-TKI was associated with the longest OS and allowed patients to avoid the potential neurocognitive sequelae of WBRT”, the researchers summarise.

“A prospective, multi-institutional randomized trial of SRS followed by EGFR-TKI versus EGFR-TKI followed by SRS at intracranial progression is urgently needed”, they add.

“Until such a study is conducted and published, the standard-of-care treatment of newly diagnosed brain metastases should remain SRS followed by systemic therapy.”


Magnuson WJ, Lester-Coll NH, Wu AJ, et al. Management of brain metastases in tyrosine kinase inhibitor–naïve epidermal growth factor receptor–mutant non–small-cell lung cancer: A retrospective multi-institutional analysis. J Clin Oncol; Advance online publication 23 January 2017. DOI: 10.1200/JCO.2016.69.7144

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