IMpower010: Exploratory analysis of disease-free survival by KRAS status in patients with stage II-IIIA NSCLC treated with adjuvant atezolizumab vs best supportive care.

Abstract

8522 Background: The Phase III IMpower010 trial (NCT02486718) met its primary disease-free survival (DFS) endpoint leading to approval of atezolizumab after adjuvant platinum-based chemotherapy for completely resected PD-L1 TC ≥1% or ≥50% stage II-IIIA NSCLC in the US, EU and other regions. Mutant KRAS (mKRAS) is the most prevalent oncogenic driver in metastatic NSCLC (27% mKRAS [KRAS G12C,11%]; Osta et al, J Thorac Oncol 2019). Here, we report exploratory DFS outcomes by KRAS mutational status in patients from IMpower010. Methods: The study design and primary results of IMpower010 have been reported (Felip et al, Lancet 2021). After complete resection, patients received cisplatin-based doublet chemotherapy (1-4 21-day cycles) and were subsequently randomized to receive atezolizumab 1200 mg q3w (16 cycles) or best supportive care (BSC). This post hoc analysis evaluated DFS in subgroups of patients by KRAS mutational status. KRAS mutational status was assessed retrospectively using whole-exome sequencing (WES) on resected tumor tissue. Analyses were conducted in patients whose tumors harbored any mKRAS type, including G12C. A separate analysis of the KRAS G12C subgroup was not conducted due to limited patient numbers. Results: Of the 1005 patients in the intention-to-treat population (all randomized patients with stage IB-IIIA NSCLC), 603 comprised the WES biomarker-evaluable population (WES-BEP), and of these, 536 had stage II-IIIA NSCLC. Within the stage II-IIIA WES-BEP, the prevalence of mKRAS and KRAS G12C was 22% (n=118) and 10% (n=52), respectively. mKRAS was enriched in White, non-squamous and smoker populations. Atezolizumab showed DFS improvement vs BSC regardless of KRAS status in the stage II-IIIA WES-BEP (Table). In the mKRAS stage II-IIIA WES-BEP, atezolizumab showed DFS improvement vs BSC regardless of PD-L1 status. Conclusions: In IMpower010, the prevalence of mKRAS and KRAS G12C was similar to that seen in metastatic NSCLC. Despite limited patient numbers in this exploratory analysis, DFS appeared to be consistent and in favor of atezolizumab across subgroups regardless of KRAS status. Clinical trial information: NCT02486718 . [Table: see text]