Deferring radiotherapy to administer epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) first doesn’t prolong overall survival, it shortens survival in patients who have brain metastases of EGFR-mutated non–small-cell lung cancer (NSCLC), according to a report in the Journal of Clinical Oncology.
Upfront therapy using EGFR TKIs such as erlotinib has been proposed as a way to avoid radiotherapy altogether in this patient population, or to at least defer it and any related toxicities until intracranial disease progresses, said William J. Magnuson, MD, of Yale University, New Haven, Conn., and his associates.
To assess the advantages and disadvantages of upfront EGFR TKIs vs. initial radiotherapy, the researchers pooled survival data for 351 patients treated at six academic medical centers during 2008-2015. A total of 131 (37%) received upfront EGFR TKIs followed by stereotactic radiosurgery or whole-brain radiotherapy when the brain metastases progressed, 120 (34%) received whole-brain radiotherapy followed by EGFR TKIs, and 100 (29%) received stereotactic radiosurgery followed by EGFR TKIs. These patients were followed for a median of 22 months.
Median overall survival was 25 months for upfront EGFR TKIs, compared with 30 months for initial whole-brain radiotherapy and 46 months for initial stereotactic radiosurgery. At 2 years, overall survival rates for the three study groups were 51%, 62%, and 78%, respectively. Both forms of initial radiotherapy were associated with improved overall survival relative to EGFR TKIs, with a hazard ratio of 0.39 for stereotactic radiosurgery and a hazard ratio of 0.70 for whole-brain irradiation.
This survival advantage was even more pronounced in the subgroup of patients who had more favorable prognostic features at baseline. These patients had a median overall survival of 64 months if they received radiotherapy followed by EGFR TKIs, compared with only 32 months if EGFR TKIs were taken before radiotherapy, the investigators said (J Clin Oncol. 2017 Jan 23. doi: 10.1200/JCO.2016.69.7144).
These findings have the potential to change clinical practice, but prospective randomized data to confirm the results are urgently needed. “Until such a study is conducted and published, the standard-of-care treatment of newly diagnosed brain metastases should remain stereotactic radiosurgery followed by systemic therapy,” Dr. Magnuson and his associates said.
No funding source was cited for this study. Dr. Magnuson reported having no relevant financial disclosures; his associates reported having ties to numerous industry sources.