Real-world characteristics and outcomes of ERBB2-mutant NSCLC in Latin American patients (CLICaP)

Abstract

Introduction:ERBB2-mutant non-small cell lung cancer (NSCLC) represents approximately 1%-4% of all lung adenocarcinomas (LUADs) and has emerged as a distinct molecular subtype. Little is known about NSCLC harboring ERBB2 mutations in Latin America. This study aimed to characterize the real-world clinical characteristics and outcomes of ERBB2-mutant NSCLC in Latin America. Materials and methods: Patients with NSCLC harboring ERBB2 mutations detected by next-generation sequencing in tumors or cfDNA were identified in databanks from 3 Latin American countries (Brazil, Colombia, and Mexico). Demographic, clinical, and pathological data were retrieved from electronic medical records. Results: Of 1245 patients with NSCLC included from January 2015 to September 2022, 35 (2.8%) patients had tumors with ERBB2 mutations. The median age was 60 years (IQR: 49-69), 54.2% of patients were females, 59.4% were never smokers, 51.3% had baseline performance status ECOG 0, 91.5% were diagnosed with stage IV disease, and 29.7% had de novo brain metastasis. The most common ERBB2 mutations were A775_G776insYVMA (40%) and G780_P781dupGSP (20%). The most often co-mutated gene was TP53 (17.1%), and the median tumor mutation burden was 2 mut/Mb (IQR: 1-4). PD-L1 tumor proportion score was ≥50%, 1%-49%, and <1% in 11.4%, 54.2%, and 31.4%, respectively. Regarding treatment patterns, 74.2% of patients received chemotherapy (CT) plus immune checkpoint blockade (ICB) in the first line, and 42.8% received antibody-drug conjugates (ADC) targeting ERBB2 in further lines of therapy, especially trastuzumab emtansine (37.1%) and trastuzumab deruxtecan (5.7%). The median real-world progression-free survival (rwPFS) to the first line was 6.7 months (95%CI, 5.65-8.48). The median real-world overall survival (rwOS) for the entire cohort was 25.9 months (95% CI, 24.4-27.9). Conclusion: This study demonstrated that ERBB2-mutant NSCLC is uncommon among Latin American patients. Despite the vast majority of patients being treated with chemo-immunotherapy (ICB) in the first line, the median rwOS was similar to that reported for non-oncogene-addicted NSCLC.