P47.18 Almonertinib With Radiotherapy vs Concurrent Chemoradiotherapy in Unresectable Stage III EGFR-mutant NSCLC (ADVANCE Trial)

For patients with unresectable stage III non-small cell lung cancer (NSCLC), the standard of care is concurrent chemoradiotherapy (CRT), and the PACIFIC trail demonstrated significant progression-free survival (PFS) and overall survival (OS) benefit with the consolidation durvalumab for those without progression. However, the number of patients with EGFR-positive mutation in the PACIFIC trial is small (6%, 43/713), and the subset analyses assessing PFS (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.40-1.75) and OS (HR 0.97, 95% CI 0.40-2.33) between durvalumab and placebo were inconclusive. Therefore, a more effective therapeutic strategy for this population needs to be further investigated. Almonertinib (HS-10296) is a novel, third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) approved in China to treat EGFR-mutant NSCLC. Based on this information, we conducted a phase III trial to assess the efficacy and safety of almonertinib with radiotherapy as a potential chemotherapy-free option in the treatment of unresectable stage III EGFR-mutant NSCLC (ChiCTR2000040590). This is the first trail to explore almonertinib and radiotherapy combination with induction EGFR-TKI in the unresectable setting. This is a multicenter, randomized, open-label, phase III trial. In total this trial aims to enroll approximately 254 patients with unresectable stage III EGFR-mutant NSCLC who have not received systemic or local antineoplastic therapy. Patients will be randomized (1:1) to receive almonertinib with radiotherapy (group A) or concurrent CRT (group B), stratified by EGFR mutation (Ex19del vs L858R). In group A, almonertinib induction therapy (110mg PO once daily) will be given for 2 months firstly, followed by almonertinib (110mg PO once daily) combined with radiotherapy (total dose 54-66 Gy, once daily, 5 times a week). In group B, radiotherapy (total dose 54-66 Gy, once daily, 5 times a week) in combination with cisplatin (75 mg/m2) plus pemetrexed (500 mg/m2) on day 1 of 21-day cycles (every 3 weeks) will be given for 3 cycles, followed by pemetrexed maintenance (500 mg/m2) every 3 weeks for 4 cycles. Patients in group B will be eligible to cross over to receive almonertinib therapy if all protocol-specified criteria are met. The primary endpoint is PFS. Secondary endpoints included OS, time to second objective disease progression (PFS2), objective response rate (ORR), duration of response (DOR), disease control rate (DCR), depth of response (DepOR), time to treatment failure (TTF), distant metastasis rate (DMR), time to metastasis and safety. Planned total treatment duration is 24 months. The first patient had been enrolled in March 2021. ▪▪▪ ▪▪▪