A multicenter phase II trial led by Sagus Sampath, MD, and his team hailing from City of Hope and UT Southwestern has demonstrated compelling evidence that consolidative radiotherapy (RT) can significantly improve outcomes for patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC) treated with osimertinib. While osimertinib is already a powerful targeted therapy, the role of moderate-dose stereotactic body radiation therapy (SBRT) and hypofractionated RT in this setting has been uncertain — until now.
The study enrolled 42 patients with exon 19 or 21 EGFR mutations and no prior targeted or immune therapy. After eight weeks of osimertinib, those with stable or responding disease were eligible for consolidative RT to up to six residual lesions, all while continuing osimertinib. Of the cohort, 76% received RT, most commonly to thoracic or bone sites. Importantly, asymptomatic brain metastases were monitored with MRI rather than immediately treated, offering a real-world glimpse into practical management.
The researchers found that with a median follow-up of nearly 43 months, three-year lesion-specific control reached 84%. Patients with baseline brain metastases achieved a median intracranial progression-free survival (PFS) of 30.2 months, far exceeding historical benchmarks for osimertinib-chemotherapy combinations. For patients without brain metastases, the median intracranial PFS had not even been reached. As Dr. Sampath explained, “the biggest impact of our work would be to make consolidative RT a routine practice for newly diagnosed EGFR patients with limited metastatic sites receiving first-line TKI treatment.”
One of the most exciting insights from the trial is that high-dose ablative regimens may not be necessary. “Lower BED regimens, such as 35 Gy/5 fractions to areas in the lung/mediastinum/hilum, and 30 Gy/3 fractions to bone, can yield high rates of long-term local control,” Dr. Sampath noted. This makes consolidative RT not only effective, but also practical for widespread adoption, as he notes, “The lower-BED regimens used in our trial are conducive to widespread adoption outside of academic centers given the consistency with meeting normal tissue constraints.”
Equally important, the trial demonstrated that patients could achieve long-lasting disease control without the added toxicity of more intensive systemic regimens. Dr. Sampath emphasized that the median CNS PFS in this study “far exceeds any single-agent osimertinib trial to date and compares similarly to more intensive systemic regimens associated with higher rates of toxicity.”
Looking ahead, the team aims to refine patient selection using molecular testing and circulating tumor DNA. As Dr. Sampath explained, the next step is “to understand which subgroups of EGFR patients would benefit from single-agent osimertinib and RT versus those requiring a more intensified systemic regimen,” such as osimertinib and chemotherapy.
This study delivers a powerful message: consolidative moderate-dose RT, paired with osimertinib, provides durable local and intracranial disease control and could redefine the standard of care for patients with EGFR-mutant NSCLC.
Abstract 132 - Consolidative Radiotherapy with Osimertinib in Advanced EGFR-Mutant Non-Small Cell Lung Cancer: Long-Term Local and Intracranial Control Results from a Phase II Trial, was presented during the SS 05 – Lung 1: NSCLC Locally Advanced and Oligometastatic session at the 67th ASTRO Annual Meeting.
