Third-generation tyrosine kinase inhibitors (TKIs), such as osimertinib, are the standard of care for frontline treatment in EGFR-altered non-small cell lung cancer (NSCLC) and penetrate the blood-brain barrier better, yielding improved intracranial responses and reduced central nervous system progression.
“But brain metastases still pose a great threat to the patient’s prognosis,” said Zhengfei Zhu, MD, PhD, who presented data comparing concurrent and consolidative cranial stereotactic radiotherapy in patients with limited brain metastases treated with osimertinib during the 2026 World Conference on Lung Cancer (WCLC) in Seoul, Republic of Korea.
The value and optimal timing of local radiotherapy-based intracranial disease control in the context of increasingly effective systemic targeted therapies for EGFR-mutant NSCLC remain uncertain, and randomized clinical trials are sparse.
As such, Dr. Zhu, deputy director of the Department of Radiation Oncology at Fudan University Shanghai Cancer Center in Shanghai, China, said further study of the clinical benefits and optimal timing of early cranial radiotherapy approaches is warranted.
Beyond the Metastatic: Redefining the Role of Local Therapy
Concurrent or Consolidative Cranial Stereotactic Radiotherapy in Osimertinib-Treated NSCLC With Limited Brain Metastases
Registered WCLC 2026 attendees can watch this session with on-demand access to WCLC recordings via the virtual platform. WATCH NOW
Dr. Zhu and colleagues performed a retrospective analysis across three academic centers in China to study the value of early cranial stereotactic radiotherapy (ecSRT) in patients with EGFR-mutant NSCLC who had received osimertinib and had limited brain metastases at baseline. Limited brain metastases were defined by the presence of 10 or fewer lesions, with the largest tumor diameter being no greater than 3 cm and a total tumor volume no greater than 15 mL. Patients who underwent SRT within a month of initiating osimertinib were considered to have received concurrent ecSRT. Patients with documented non-progressive disease who received SRT a month or longer after completing osimertinib were considered to have received consolidative ecSRT.
The investigators compared outcomes by ecSRT timing, including overall survival (OS), progression-free survival (PFS), intracranial progression-free survival (iPFS), intracranial progression patterns, and symptomatic radiation necrosis between patients who received ecSRT concurrently with osimertinib and those who received it as consolidative therapy. A propensity score matching approach was used to compare groups.
Of 403 patients, 148 (36.7%) received ecSRT, while the remaining 255 received osimertinib alone. Patients who received ecSRT had improved iPFS, PFS, and OS compared with those who received osimertinib alone, Dr. Zhu said.
Time-dependent Cox regression and landmark analyses also showed reduced incidence of cumulative intracranial progression, especially local intracranial progression, as well as improved iPFS and PFS, with incorporation of ecSRT, compared with osimertinib treatment alone, suggesting a benefit for ecSRT in this setting. Although iPFS and PFS were longer with consolidative ecSRT than with osimertinib alone, consolidative ecSRT did not confer a significant OS benefit.
When patients were stratified by response to osimertinib, ecSRT did not improve outcomes among those who achieved complete response to osimertinib therapy. Consolidative ecSRT improved iPFS, PFS, and OS in patients who did not obtain intracranial complete response (iCR) to osimertinib, suggesting a benefit for ecSRT in this subset.
Based on these findings, Dr. Zhu concluded that ecSRT may improve survival outcomes in patients with EGFR-mutant NSCLC who have limited brain metastases at baseline and receive first-line osimertinib. The benefit of ecSRT was response-dependent, Dr. Zhu said, with OS benefit for patients who had residual cranial disease after osimertinib, especially with the consolidative SRT approach.
“Assessment of intracranial response after initial osimertinib may help identify patients most likely to benefit from consolidative SRT,” Dr. Zhu said.
