IMpower010: Genomic profiling and clinical outcomes with adjuvant atezolizumab in early-stage non-small cell lung cancer (eNSCLC).

Abstract

8022 Background: In metastatic NSCLC (mNSCLC), genomic alterations (MUT) are well studied and have led to the development of efficacious new drugs. However, the association of MUT in the adjuvant setting in eNSCLC is not as well understood. Here, we describe an exploratory, retrospective analysis of genomic profiling by whole exome sequencing and clinical association in IMpower010. Methods: Whole exome sequencing was done on baseline tumor samples and germline DNA from whole blood from the biomarker-evaluable population (n=623). Multiple MUT were identified in the full population, including by histology. Disease-free survival (DFS) and overall survival (OS) were assessed in the most common gene subgroups. Results: The distribution of MUT and co-occurrence patterns were similar to expected non-squamous and squamous patterns in mNSCLC, except for lower prevalence of STK11 (17%) and KEAP1 (12%) MUT. In non-squamous disease, STK11 , EGFR , and KEAP1 MUT were associated with increased prevalence in PD-L1–negative tumors, and TP53 MUT with PD-L1–positive tumors (adjusted P <0.1). KRAS MUT were associated with Stage II; STK11 MUT were associated with Stage I more than with Stages II and III (adjusted P <0.1). Increased enrichment of KRAS , STK11 , KEAP1 , and TP53 MUT was seen in those with previous or current smoking status, and EGFR MUT were enriched in those who never smoked (adjusted P <0.1). In non-squamous disease, STK11 MUT were a poor prognostic for OS but not DFS, whereas KEAP1 MUT were not significantly associated with poor prognosis for DFS or OS (Table). Neither STK11 or KEAP1 MUT were significantly associated with differential atezolizumab vs best supportive care DFS or OS benefit (interaction P >0.05). Conclusions: This analysis represents the largest dataset evaluating the genomic profile of patients with eNSCLC who were treated with cancer immunotherapy. The prevalences of STK11 and KEAP1 MUT were lower than in mNSCLC and were enriched for PD-L1–negative in non-squamous NSCLC. Unlike in mNSCLC, patients with tumors that harbored KEAP1 MUT did not have poor prognosis in IMpower010. Data are hypothesis generating and require validation in independent eNSCLC datasets with larger numbers. Clinical trial information: NCT02486718 . STK11 and KEAP1 associations with DFS and OS in combined arms (non-squamous). STK11 MUT STK11 WT KEAP1 MUT KEAP1 WT n 71 342 49 364 DFS Median, mo 43.1 41.8 45.3 41.8 HR (95% CI) 1.03 (0.73, 1.46) 0.91 (0.60, 1.39) OS Median, mo NR NR NR NR HR (95% CI) 1.66 (1.10, 2.52) 1.08 (0.63, 1.85) CI, confidence interval; mo, month; NR, not reached; WT, wild type.