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Background
News — Despite high response rates to EGFR inhibitors, patients with advanced EGFR mutant NSCLC generally experience disease progression within two years (osimertinib median PFS 18.9 months, median OS 38.6 months). We sought to determine whether administration of SABR to residual sites of disease at the time of expected best response to EGFR inhibition could prolong disease control.

Methods:
This was a multi-center single-arm phase 2 study. Eligible patients had advanced EGFR mutant (exon 19 or 21) NSCLC not restricted by number, site, or size of metastases; ECOG 0-2; no prior treatment with EGFR inhibitors or immune checkpoint inhibitors; and no history of interstitial lung disease. Patients with stable or responding disease after 8 weeks of osimertinib received SABR to persisting lesions, followed by continued osimertinib until progression or intolerance. At subsequent progression, patients could receive further SABR and continue osimertinib if deemed clinically feasible and appropriate. The primary endpoint was progression-free survival (PFS); secondary endpoints included duration on osimertinib, toxicity, and overall survival (OS).

Results:
A total of 43 patients (32 women, 11 men) were enrolled and initiated osimertinib, of whom 29 (67%) received SABR. Reasons SABR was not administered included
inadequate response (9%), insufficient residual disease (19%), and other (5%). At a median follow-up of 35.7 months (95% CI, 28.8, 37.6), 42 evaluable patients had a
median PFS of 32.6 months and a median OS of 45.7 months. The median duration of osimertinib was 31.5 months. Grade ≥3 toxicities included one incidence each (2%) of the following: pain at the site of radiation, paronychia, liver enzyme elevation, fatigue, hyponatremia, diarrhea, and pneumonitis.

Conclusions:
Osimertinib plus consolidative SABR appears to provide a PFS and OS benefit when considered against historical data with osimertinib alone. This treatment strategy may
offer a well-tolerated and practical approach to improving outcomes for patients with advanced EGFR mutant NSCLC.