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

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. 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. 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). 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.