Abstract 5900: ERBB2 alteration with or without co-existent EGFR mutation in metastatic non-small cell lung cancer

Background: For epidermal growth factor (EGFR) mutated non-small cell lung carcinoma (NSCLC) multiple EGFR tyrosine kinase inhibitors (TKIs) are approved. ERBB2 alteration (mutation and/or amplification) has been commonly reported as a resistance mechanism to EGFR TKIs. Here we report the prevalence of ERBB2 alteration with or without EGFR mutation in NSCLC. Methods: We retrospectively analyzed ERBB2 alterations and EGFR mutations in NSCLC patients who underwent next-generation sequencing (NSG) with Caris Life Sciences. We obtained de-identified clinical information and molecular testing results from the Caris database. The objectives were to determine the prevalence and types of ERBB2 alterations with and without EGFR as a co-mutation. Results: A total of 12946 NSCLC tumors having EGFR and/or ERBB2 NGS were available, of which 50.1% were male. Among them, 12491 patients had copy number alteration (CNA) data available for ERBB2. 1551 (12%) patients had EGFR mutation, of whom 68% were female, the median age was 68 years and 89% of patients had adenocarcinoma. 186 patients had 2 or more EGFR mutations. The most common EGFR mutation was exon 19 in 47% of patients, followed by exon 21 in 33% of patients. 321 patients (2.5%) had ERBB2 alteration (mutation and/or amplification). Among them ERBB2 was mutated in 197 patients (1.5%) and amplified in 134 (1.1%) patients. The median age of ERBB2 mutated patients was 65 years. Sixty two percent were female and 84% had adenocarcinoma. None of the patients had multiple ERBB2 mutations. 70.5% of ERBB2 mutations were in exon 20, while 10.1% in exon 8. 24 patients had concurrent EGFR mutation and ERBB2 alteration (8 had ERBB2 mutation and 16 had ERBB2 amplification). Among 8 patients who had both EGFR and ERBB2 mutations, 3 had EGFR mutation in exon 19 (E746-A750del) and exon 8 ERBB2 mutation (S310F). For the remaining 5 patients, EGFR mutation was in exon 21 (L858R), while ERBB2 mutations included exon 8 (S310F) in 3 patients, exon 8 (S310Y) in 1 patient, and exon 17 (G660D) in 1 patient. Conclusion: A minority of EGFR mutated NSCLC patients had ERBB2 alterations. In ERBB2 and EGFR co-mutated patients, exon 21 mutations for EGFR and exon 8 mutations for ERBB2 were common. Forty percent of patients who had exon 8 ERBB2 mutation had EGFR as a co-mutation. Citation Format: Vijendra Singh, Yasmine Baca, Seongho Kim, Yanis Boumber, Hirva Mamdani, Edward S. Kim, Ammar Sukari, Chul Kim, Gerold Bepler, Stephen V. Liu, Alexander I. Spira, Hossein Borghai, Mikaso Nagasaka. ERBB2 alteration with or without co-existent EGFR mutation in metastatic non-small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5900.