143P - Efficacy and safety of aumolertinib (AUM) with radiotherapy versus concurrent chemoradiotherapy (cCRT) in the treatment of unresectable stage III EGFR-mutant NSCLC: A multicenter, randomized, open-label phase III study (ADVANCE)

Background

The PACIFIC subgroup analysis indicates that immune consolidation therapy may not be beneficial for patients (pts) harboring EGFR mutations. Our prior large retrospective multicenter study showed that combining radiotherapy with targeted therapy outperformed chemoradiotherapy (CRT). Here, we firstly conduct a multicenter randomized controlled phase III study to evaluate the benefits of AUM, a third-generation EGFR-TKI, and radiotherapy instead of cCRT for unresectable stage III EGFR-mutant NSCLC.

Methods

Eligible pts were aged 18-75 years old, histologically confirmed as unresectable stage III EGFR-mutant NSCLC, who were randomized into experimental group (Group A) and control group (Group B). Group A: AUM (110mg PO QD) for 9 weeks as induction therapy, followed by radiotherapy (60 Gy) +AUM, and AUM maintenance therapy. Group B: Radiotherapy (60Gy)+Cisplatin (75 mg/m²) + Pemetrexed (500 mg/m²) Q3W for 2 cycles, followed by Pemetrexed+ Cisplatin Q3W for 1-2 cycles. After progression in Group B, crossover to Group A was allowed. The primary endpoint was PFS. Partial secondary endpoints included OS, safety and quality of life.

Results

40 pts (ITT) were enrolled, with 24 pts in Group A and 16 pts in Group B. At data cut-off (Dec,2023), the hazard ratio (HR) for PFS was 0.152 [95%CI 0.040-0.0579; p=0.0002]. The mPFS was NR for Group A vs 6.2 months for Group B, with the median follow-up time 11.2m vs 5.7m. The 12-months PFS rate was 87.0% in Group A. In Group B, eight pts had progressed. Of these pts, 4/8 (50%) had crossed over, while 3/8 (37.5%) of the pts did not, and 1/8 (12.5%) had died. OS was not reached. Grade 3 or higher (G3+) AEs occurred in 4.2% of Group A and as high as 25% of Group B. The most common TRAEs were muscular pain (12.5%; grade 1/2) and cough (8.3%; grade1), versus myelosuppression (27%; grade 3, 13%) and vomiting (13%, grade 2), respectively.

Conclusions

For pts with unresectable EGFR-mutated stage III NSCLC, the combination of AUM and radiotherapy provides better PFS benefit versus cCRT with fewer symptomatic AEs. Our study is still ongoing to extend the follow-up period to determine longer-term outcomes.

Clinical trial identification

ChiCTR2000040590.

Legal entity responsible for the study

The authors.

Funding

Self-financing and partial sponsorship of Jiangsu Haosen Pharmaceutical Group Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.