A phase II study of atezolizumab combined with cisplatin and vinorelbine as adjuvant therapy for completely resected non-small cell lung cancer with EGFR mutation (WJOG11719L: ADJUST study).

Abstract

e20004 Background: Early-stage non-small cell lung cancer (NSCLC) is known to have a different tumor microenvironment compared with advanced disease, which may enhance the efficacy of immune-checkpoint inhibitor (ICI) in the adjuvant setting. The subset analysis of IMpower010 study suggested that adjuvant ICI may have activity even in patients with EGFR mutation. Here, we conducted the phase II study and biomarker analysis of ICI combined with chemotherapy as adjuvant therapy for completely resected NSCLC harboring EGFR mutation. Methods: In this multicenter, single-arm, phase Ⅱ study, patients with completely resected NSCLC harboring EGFR mutation were enrolled. The patients received cisplatin (80 mg/m 2 ), vinorelbine (25 mg/m 2 ), and atezolizumab (1200 mg/body) for four cycles, followed by atezolizumab up to one year. The primary endpoint was disease-free survival (DFS) at two years. The secondary endpoints were DFS, overall survival (OS) and safety. A total of 18 cases were planned with the threshold and the expected DFS at two years of 55% and 80%, with one-sided α = 0.10 and β = 0.20. Using archival tumor tissues, comprehensive mutational and expression analyses were performed using Oncomine Tumor Mutation Load Assay and NanoString PanCancer IO 360 Panel. (Trial identification no. JapicCTI-194849). Results: Between August 2019 and August 2021, 18 patients were enrolled. Of those, the median age was 67, male/female: 7/11, never-/smoker: 10/8, ECOG PS 0/1: 12/6, pathological stage II/III: 6/12, and EGFR ex19 DEL/ex21 L858R: 10/8. The DFS rate at two years was 44.4% (80% confidence interval (CI): 29.4%-59.5%). The median DFS was 21 months (95%CI 13 months – not reached). Between ex19 DEL and L858R groups, DFS showed no significant difference (median, 18.5 vs 30.1 months; P = 0.99). OS rate at one, two, and three years were 100%, 83%, and 77%, respectively. Seven patients discontinued study treatment due to AEs. Severe immune-related AEs were reported in 28% of patients. Frequently detected co-alterations were: TP53 (39%), PIK3CA (17%), ARID2 (11%), SMAD4 (11%), and PTEN (11%), respectively. Elevated expression levels of gene sets associated with lymphoid compartment, JAK-STAT signaling and hypoxia were associated with favorable efficacy. Conclusions: Although atezolizumab combined with cisplatin plus vinorelbine is feasible, this regimen did not improve DFS in patients with completely resected NSCLC harboring EGFR mutation. Further studies are needed to identify predictive biomarkers for propelling precision medicine. Clinical trial information: JapicCTI-194849 .