Clinical characteristics, genomic features, and recurrence risk of early-stage MET exon 14 mutant non-small cell lung cancer (NSCLC).

Abstract

9042 Background: MET exon 14 alterations occur in ~3% of patients (pts) with NSCLC. Although clinical and genomic features of MET exon 14 mutant (mut) NSCLC are better characterized in the metastatic setting, less is known about early-stage disease for this molecular subtype. Methods: Clinicopathologic and genomic data were collected from patients (pts) with resected stage I-III MET exon 14 mutant NSCLC at the Dana-Farber Cancer Institute (DFCI) and the Memorial Sloan Kettering Cancer Center (MSKCC). We estimated the disease-free survival (DFS) and overall survival (OS) of patients from the date of surgical resection. The prevalence of MET exon 14 mutations in stage I-III NSCLC was assessed using OncoPanel NGS v3.0 at DFCI. Results: The prevalence of MET exon 14 alterations in resected tumors of pts with stage I-III NSCLC at DFCI using Oncopanel v3 was 2.8% (17/613) overall: 2.9% (16/542) in non-squamous and 1.4% (1/71) in squamous histology. We identified 131 pts with resected stage I-III (I = 73, II = 28, III = 30) MET exon 14 mut NSCLC at DFCI (Oncopanel v1-v3) and MSKCC (MSK-IMPACT), with a median age of 71 years (yrs) (range: 43-88). There were no significant differences in sex, smoking status, or type of MET alteration across stages. In stage I resected tumors there was a higher proportion of adenocarcinoma histology compared to stages II and III (p = 0.009). The median harmonized TMB (mTMB) was similar across stages (p = 0.43). Common genomic co-alterations included MET amplification (amp) (5.3%), CDK4/ 6 amp (19.1%), MDM2 amp (35.1%), TP53 mut (17.6%) and CDKN2A/ B loss (9.2%). The median DFS in stage I, II, and III NSCLC was 8.3 yrs (95% CI: 3.1-8.3), 2.6 yrs (95% CI: 1.0-2.6), and 2.1 yrs (95% CI: 0.7-2.7), respectively (p = 0.017). The median OS in stage I, II, and III NSCLC was 9.2 yrs (95% CI: 8.5 -10.5), not reached (NR) (95% CI: NR-NR), and 4.1 yrs (95% CI: 3.6-4.1), respectively (p = 0.052). Concurrent MET amp was independently associated with worse DFS (HR: 4.9, 95% CI: 1.8-13.1; p = 0.002) in multivariate analysis. Conclusions: MET exon 14 mutations are present in 2.8% of resected stage I-III NSCLCs. Given the prevalence of this molecular alteration in early-stage NSCLC, clinical trials exploring the role of adjuvant and neoadjuvant MET targeted therapies in this population may be warranted.