Abstract：
BACKGROUND: Third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have significant antitumor activity to advanced non-small-cell lung cancer (NSCLC) patients with classic EGFR mutations. However, EGFR-TKI monotherapy shows poor efficacy in patients whose circulating tumor cell DNA (ctDNA) of EGFR mutations cannot be rapidly cleared.
METHODS: As a third-generation TKI, furmonertinib has shown superior antitumor activity and minor toxicity. The FOCUS-C study is a prospective, multicenter, randomized controlled trial (NCT05334277) to explore the efficacy and safety of furmonertinib plus pemetrexed-platinum doublet chemotherapy with or without bevacizumab versus furmonertinib monotherapy in untreated advanced EGFR mutant NSCLC patients without EGFR clearance after the induction therapy of furmonertinib. Patients with EGFR clearance will still receive furmonertinib as Arm A. Patients without ctDNA clearance will be randomized in a 2:2:1 ratio as Arm B1 (furmonertinib), Arm B2 (furmonertinib combined with carboplatin and pemetrexed for 4 cycles, and then furmonertinib and pemetrexed as maintenance therapy) and Arm B3 (Arm B2 regimen plus bevacizumab). The primary endpoint is progression-free survival (PFS) in Arm B2/B1. Secondary endpoints include PFS in Arm B3/B1, PFS in Arm A/B1, PFS in Arm B3/B2, objective response and disease control rate, overall survival and safety in all Arms. Exploratory endpoints are focused on the efficacy based on plasma NGS at different timepoints.
CONCLUSIONS: This study will evaluate the efficacy and tolerability of furmonertinib plus carboplatin and pemetrexed with or without bevacizumab verses furmonertinib alone in untreated patients with advanced EGFR mutant NSCLC without EGFR clearance.
METHODS: As a third-generation TKI, furmonertinib has shown superior antitumor activity and minor toxicity. The FOCUS-C study is a prospective, multicenter, randomized controlled trial (NCT05334277) to explore the efficacy and safety of furmonertinib plus pemetrexed-platinum doublet chemotherapy with or without bevacizumab versus furmonertinib monotherapy in untreated advanced EGFR mutant NSCLC patients without EGFR clearance after the induction therapy of furmonertinib. Patients with EGFR clearance will still receive furmonertinib as Arm A. Patients without ctDNA clearance will be randomized in a 2:2:1 ratio as Arm B1 (furmonertinib), Arm B2 (furmonertinib combined with carboplatin and pemetrexed for 4 cycles, and then furmonertinib and pemetrexed as maintenance therapy) and Arm B3 (Arm B2 regimen plus bevacizumab). The primary endpoint is progression-free survival (PFS) in Arm B2/B1. Secondary endpoints include PFS in Arm B3/B1, PFS in Arm A/B1, PFS in Arm B3/B2, objective response and disease control rate, overall survival and safety in all Arms. Exploratory endpoints are focused on the efficacy based on plasma NGS at different timepoints.
CONCLUSIONS: This study will evaluate the efficacy and tolerability of furmonertinib plus carboplatin and pemetrexed with or without bevacizumab verses furmonertinib alone in untreated patients with advanced EGFR mutant NSCLC without EGFR clearance.
摘要：
背景：第三代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）对EGFR突变的晚期非小细胞肺癌（NSCLC）患者具有显著的抗肿瘤活性。然而,EGFR-TKI单药治疗在不能快速清除EGFR突变的循环肿瘤细胞DNA（ctDNA）的患者中显示疗效差。
方法：作为第三代TKI，furmonertinib具有优异的抗肿瘤活性和较小的毒性。FOCUS-C研究是一项前瞻性的,多中心，随机对照试验(NCT05334277)探讨在未治疗的晚期EGFR突变型NSCLC患者中,在接受furmonertinib诱导治疗后未清除EGFR的情况下,联合或不联合贝伐单抗治疗的furmonertinib联合培美曲塞-铂双联化疗与furmonertinib单药治疗的疗效和安全性.EGFR清除的患者仍将接受furmonertinib作为A组。没有ctDNA清除的患者将以2：2：1的比例随机分配为B1组（furmonertinib）。组B2（furmonertinib联合卡铂和培美曲塞4个周期，然后用furmonertinib和培美曲塞作为维持治疗）和B3组（B2组方案加贝伐单抗）。主要终点是B2/B1组的无进展生存期（PFS）。次要终点包括B3/B1臂的PFS，A/B1臂的PFS，B3/B2臂的PFS，客观反应和疾病控制率，所有武器的总体生存和安全。探索性终点集中在基于不同时间点的血浆NGS的功效上。
结论：这项研究将评估在未经治疗的晚期EGFR突变型NSCLC无EGFR清除患者中，使用或不使用贝伐单抗与单独使用furmonertinb联合卡铂和培美曲塞的疗效和耐受性。
方法：作为第三代TKI，furmonertinib具有优异的抗肿瘤活性和较小的毒性。FOCUS-C研究是一项前瞻性的,多中心，随机对照试验(NCT05334277)探讨在未治疗的晚期EGFR突变型NSCLC患者中,在接受furmonertinib诱导治疗后未清除EGFR的情况下,联合或不联合贝伐单抗治疗的furmonertinib联合培美曲塞-铂双联化疗与furmonertinib单药治疗的疗效和安全性.EGFR清除的患者仍将接受furmonertinib作为A组。没有ctDNA清除的患者将以2：2：1的比例随机分配为B1组（furmonertinib）。组B2（furmonertinib联合卡铂和培美曲塞4个周期，然后用furmonertinib和培美曲塞作为维持治疗）和B3组（B2组方案加贝伐单抗）。主要终点是B2/B1组的无进展生存期（PFS）。次要终点包括B3/B1臂的PFS，A/B1臂的PFS，B3/B2臂的PFS，客观反应和疾病控制率，所有武器的总体生存和安全。探索性终点集中在基于不同时间点的血浆NGS的功效上。
结论：这项研究将评估在未经治疗的晚期EGFR突变型NSCLC无EGFR清除患者中，使用或不使用贝伐单抗与单独使用furmonertinb联合卡铂和培美曲塞的疗效和耐受性。
