Early cranial stereotactic radiotherapy (SRT) administered with first-line osimertinib was associated with improved intracranial control and survival outcomes in patients with EGFR-mutant non-small cell lung cancer (NSCLC) and limited brain metastases, according to research presented at the International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC).
The retrospective study evaluated patients with EGFR-mutant NSCLC and baseline limited brain metastases who were treated with first-line osimertinib, comparing outcomes among those who received early cranial SRT with those treated with osimertinib alone. The analysis also examined the timing of SRT and whether patients achieved an intracranial complete response to osimertinib.
"These findings suggest that the benefit of adding cranial stereotactic radiotherapy to first-line osimertinib may depend on how the intracranial disease responds to systemic therapy," said Zhengfei Zhu, MD, PhD, Department of Radiation Oncology, Fudan University Shanghai Cancer Center, in Shanghai, China. "Patients who do not achieve an intracranial complete response with osimertinib may be particularly appropriate candidates for consolidative SRT."
Among patients treated with osimertinib alone, 60 of 255 patients (23.5%) achieved an intracranial complete response. Patients who did not achieve an intracranial complete response appeared to derive the greatest overall survival benefit from SRT, particularly when SRT was administered in a consolidative manner. In contrast, no clear overall survival benefit from SRT was observed among patients who achieved an intracranial complete response.
Compared with osimertinib alone, consolidative SRT was associated with improved overall survival, while concurrent SRT was not associated with a statistically significant overall survival improvement. The study also reported 1-year, 2-year and 3-year cumulative incidences of symptomatic radiation necrosis of 9.3%, 24.0% and 28.2%, respectively.
The researchers concluded that early cranial SRT may improve intracranial control and survival outcomes when integrated with first-line osimertinib for patients with EGFR-mutant NSCLC and limited brain metastases. The results support a response-adapted approach in which patients without an intracranial complete response to osimertinib may be considered for consolidative cranial SRT, while the survival benefit may be less clear for patients who achieve a complete intracranial response.
Based on these findings, a randomized clinical trial (NCT06020066) evaluating the clinical value of consolidative SRT in this patient population is ongoing.
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