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

03:20pm - 03:30pm PT

Room 156/158

Presenter(s)

Sagus Sampath, MD - City of Hope Medical Center, Duarte, CA

S. Sampath¹, K. D. Westover², K. Pithadia², S. Rashdan³, A. Gao⁴, S. Zhang⁵, and D. E. Gerber⁶; ¹Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, ²Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, ³UT Southwestern Medical Center, Dallas, TX, United States, ⁴Department of Population and Data Sciences, University of Texas Southwestern Medical Center, Dallas, TX, ⁵UT Southwestern Medical Center, Dallas, TX, ⁶University of Texas Southwestern Medical Center, Dallas, TX

Purpose/Objective(s): The long-term efficacy of moderate-dose stereotactic body radiation therapy (SBRT) and hypofractionated radiotherapy (RT) in EGFR-mutant non-small cell lung cancer (NSCLC) patients receiving osimertinib remains unclear. We report local lesion control and intracranial progression-free survival (PFS) from a phase II study.

Materials/Methods: This multicenter, single-arm phase II trial enrolled patients with advanced EGFR-mutant (exon 19 or 21) NSCLC. Eligibility criteria included: ECOG 0-2, no prior EGFR-targeted therapy or immunotherapy, and no restrictions on metastatic burden. Patients showing stable disease or response after 8 weeks of osimertinib received RT to up to 6 persistent lesions, followed by continued osimertinib. Asymptomatic brain metastases at diagnosis were monitored with quarterly MRI without RT. RT dosing followed NRG LU-002 trial protocol. Endpoints were analyzed using Kaplan-Meier methods, excluding deaths as competing events.

Results:

Of 42 enrolled patients, 32 (76%) received RT. The primary reason for not receiving RT was insufficient residual disease (10%). Twenty-one patients (50%) presented with brain metastases (median 3 lesions, range 1-15). RT was delivered to 1, 2, 3, and 4 lesions in 18 (43%), 10 (24%), 2 (5%), and 2 (5%) patients, respectively. Common RT regimens for thoracic lesions (n=31) included (Gy/number of fractions, n, %): 35/5, 7, 23; 34/5, 5, 16; 30/3, 5, 16; and 45/15, 4, 13. For bone lesions (n=13): 30/3, 4, 31; 25/5, 2, 15; 34/5, 2, 15; and 27/3, 2, 15.

At median follow-up of 42.8 months (95% CI: 21.9-54.7), 3-year lesion-specific control was 84% (95% CI: 66-93%). Six local failures occurred, with four receiving hypofractionated doses (45 Gy/15 fractions, n=3; 30 Gy/10 fractions, n=1). Median intracranial PFS was 30.2 months (95% CI: 10.8-not reached) in patients with baseline brain metastases, versus not reached in those without (p=0.008). Fourteen patients received RT for oligoprogression (brain: 4, bone: 4, regional nodes: 3, lung: 2, liver: 1) at median 20.6 months from trial enrollment, with 7 patients remaining alive on osimertinib.

Conclusion: Moderate-dose SBRT following initial osimertinib therapy yielded excellent long term local control, with follow-up time exceeding other comparable trials. Ablative regimens with higher biological effective dose may not be required in both the consolidation and oligoprogression setting. Higher local failure observed with hypofractionation warrants further analysis. Notably, outcomes for patients with baseline brain metastases surpassed historical benchmarks for osimertinib-chemotherapy combinations.