Dr Liu on the Frequency of Activating ERBB2 and ERBB3 Alterations in NSCLC

Dazhi Liu, PharmD, MS, BCOP, clinical pharmacy specialist III, Early Drug Development Service, Memorial Sloan Kettering Cancer Center, discusses findings from a real-world analysis of the frequency of ERBB2 and ERBB3 alterations in patients with non–small cell lung cancer (NSCLC) and the efficacy of liquid vs tissue biopsies for detecting these alterations, which she presented at the IASLC World Conference on Lung Cancer.

Liu and colleagues conducted a real-world landscape analysis of activating ERBB2 and ERBB3 alterations in 107,561 tissue and plasma samples from patients with NSCLC. Among the included tissue samples (n = 96,910), the frequency of ERBB2 mutations was 1.7%, the frequency of ERBB2 amplifications was 1.9%, and the frequency of both mutations and amplifications was 0.2%. These findings were consistent with findings from previous studies with smaller sample sizes, Liu notes. This study also had the largest sample size in which the frequency of ERBB3 alterations was investigated, Liu says. The frequencies of ERBB3mutations and amplifications were 0.3% and 0.5%, respectively.

This was also the first study of its sample size to compare frequencies of ERBB2 and ERBB3 alterations across both tissue and liquid biopsy results, Liu explains. The frequency of HER2 mutations in the liquid biopsy samples was consistent with that in the tissue biopsy samples, at 1.7%. However, the frequency of HER2 amplification in the liquid biopsy samples was lower than in tissue biopsy samples, at 0.3% vs 1.9%, respectively. These findings indicate that liquid biopsy does not catch all instances of HER2 amplification, likely because of the low circulating tumor DNA (ctDNA) tumor fraction of liquid biopsy, according to Liu. A separate analysis conducted by Foundation Medicine showed that the incidence of HER2 amplifications in liquid biopsy samples was higher in patients with higher ctDNA tumor fraction. Therefore, catching HER2 amplifications through liquid biopsy depends on high ctDNA tumor fraction, Liu concludes.

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