Director Boehringer Ingelheim Pharmaceuticals Incorporated, Ridgefield, CT, USA, United States
Background: Prognosis of advanced non-small cell lung cancer (NSCLC) continues to be poor. A better understanding of the epidemiology of NSCLC with human epidermal growth factor receptor 2 (HER2) mutations is needed to further develop effective therapies based on molecular and genomic subtypes. Prior studies have been small ( < 100 patients) and often focused on specific HER2 mutations.
Objectives: To understand the prevalence and characteristics of patients with advanced/metastatic NSCLC with HER2 mutations based on comprehensive genomic profiling (CGP) with next-generation sequencing (NGS).
Methods: This noninterventional study used the nationwide (US-based) deidentified Flatiron Health-Foundation Medicine NSCLC clinico-genomic database (FH-FMI CGDB). Data come from electronic health records from approximately 280 cancer centers linked to genomic data derived from FMI CGP tests by deidentified, deterministic matching. Adults (≥18 years) with advanced (IIIB, IIIC) or metastatic (IV, IVA, IVB) NSCLC diagnosed from 1 January 2015 to 31 March 2021 were selected. Descriptive analyses were performed. No specific exposures or clinical outcomes were analyzed.
Results: Of 11,794 adults diagnosed with advanced or metastatic NSCLC, 550 patients had a HER2 mutation. The prevalence of HER2 mutation was 4.7% (95% CI: 4.3-5.1%). Of the patients with HER2 mutations, 89.5% were at a community practice, 50.2% were female, 69.2 years was the median age at diagnosis (interquartile range [IQR], 61.8-76.3), and 25.4% were never-smokers. Most patients were White (65.3%), with 6.9% Black or African American, 4.7% Asian, and 16.5% reporting other race categories; race data were missing/unknown for 6.5%. Most patients had advanced/metastatic NSCLC at initial diagnosis (65.1% stage IV; 16.4% stage III); 80% had nonsquamous disease. At baseline, 68.2% had an Eastern Cooperative Oncology Group performance status of 0-1, and 17.8% had brain metastases. Among 450 patients treated, median time from diagnosis to first-line (1L) treatment was 40 days (IQR, 26-66 days). Most received only 1L or second-line (2L) treatment (1L: n=195 [42.9%]; 2L: n=129 [28.4%]).
Conclusions: This is one of the largest real-world studies of patients with HER2-mutated NSCLC in the US based on NGS testing, which can detect a broad range of alterations. It further elucidates the epidemiology of advanced/metastatic NSCLC with HER2 mutations. A potential limitation is that the data source only includes patients with genomic data from the FH-FMI CGDB; however, the characteristics of NSCLC patients in this source are generally similar to other US data sources, such as the Surveillance, Epidemiology, and End Results Program. Future analyses of patient characteristics and outcomes by HER2 mutations would be important.
