Survival of induction aumolertinib followed by aumolertinib and concurrent radiotherapy (RT) in unresectable EGFR -mutated stage III NSCLC: Final analysis of the phase III ADVANCE trial and real-world data.

8048 Background: The LAURA trial established concurrent chemoradiotherapy (cCRT) followed by consolidation targeted therapy as the standard for unresectable stage III EGFR-mutated non-small cell lung cancer (NSCLC). The phase III ADVANCE trial (ChiCTR2000040590) evaluated induction aumolertinib followed by aumolertinib and concurrent RT versus cCRT. Methods: Eligible patients (pts) aged 18-75 with unresectable stage III non-squamous NSCLC and centrally confirmed EGFR exon 19 deletion or L858R mutation were randomized 1:1 to receive aumolertinib+RT (experimental) or cCRT (control). The primary endpoint was progression-free survival (PFS), assessed by investigator. The accrual target was 98 pts, aiming for a hazard ratio (HR) of 0.5 (80% power, one-sided α =0.025). A real-world database (RWD; NCT04304638) from 6 trial sites was developed to validate long-term survival outcomes for pts treated with RT and third-generation EGFR TKIs. Results: Between March 2021 and March 2024, 43 eligible pts were randomized (24 to experimental, 19 to control) following early termination due to feasibility issues. At a median follow-up of 25.5 months (mo), the experimental group showed significantly longer PFS (34.0 vs. 7.8 mo; HR 0.15, 95% CI 0.06–0.24). Median overall survival (OS) was not reached in the experimental group but was 30.5 mo in the control (p = 0.17). The control group reported more neutropenia (52.6% vs. 16.7%, p = 0.01) and nausea (26.3% vs. 0.0%, p = 0.03), while quality of life was better in the experimental group. Among 18 experimental and 16 control pts completing RT without progression, the experimental group had significantly longer PFS (not reached vs. 12.8 mo; HR 0.05, 95% CI 0.01–0.16) and OS (HR 0.09, 95% CI 0.01–0.68). From 2012 to 2024, 125 consecutive pts were included in the RWD cohort: 31 in RT + TKI, 33 in CRT + TKI, and 61 in CRT. At a median follow-up of 32.7 mo, PFS and OS were significantly longer in RT + TKI and CRT + TKI compared to CRT (PFS: not reached vs. 36.7 vs. 9.8 mo; OS: not reached vs. not reached vs. 48.9 mo; p < 0.001). No significant differences in PFS and OS were observed between RT + TKI and CRT + TKI (p=0.59 and 0.80, respectively). Conclusions: The ADVANCE trial and RWD demonstrate that induction EGRF TKI followed by TKIs and RT delays progression and improves survival in unresectable stage III EGFR-mutated NSCLC. Clinical trial information: ChiCTR2000040590 .