Abstract 212P
Background
ERBB2 alterations are potential candidates for targeted treatments in metastatic urothelial cancer (UC). Recent data suggest that HER2-targeted antibody-drug conjugate (ADC) treatment is efficacious. Here, we explore the role of ERBB2 in UC by analyzing genomics in a large database of real-world patients.
Methods
Tumor tissues from 1112 Chinese patients with UC were evaluated by comprehensive genomic profiling for alterations in 808 cancer-related genes. Results were analyzed for base substitutions, short indels, copy number changes, and selected rearrangements.
Results
Of 1112 cases, 167 (15.0%) featured ERBB2 genomic alterations (GAs), including 82 (7.4%) ERBB2 mutations (ERBB2mut), 41 (3.7%) ERBB2 amplifications (ERBB2amp) and 44 (4.0%) cases had co-occurring ERBB2 GAs. ERBB2mut was not mutually exclusive of ERBB2amp which occurred in up to 43.2% of co-altered cases. The top mutated ERBB2 SNVs/indels were p.S310F/Y (32, 21.2%) and p.L755S (7, 4.6%). ERBB2mut predominantly affected the kinase (49, 32.5%) or extracellular (69, 45.7%) domains. Genes commonly co-altered with ERBB2 were TERT (68.9%), ARID1A(37.1%), RB1 (28.7%), KMT2C (26.9%) and ATM (24.6%). Other significantly higher mutation frequency for genes were TP53, APC, SMARCA4, NF1, ERBB3, ERCC2, EGFR and MTOR (p＜0.05) in ERBB2 GAs cases. Significantly lower rates of CDKN2B were found in ERBB2 GAs compared with ERBB2 wild type (22.0% vs 12.0%, p＜0.01). CDK12 was the most common co-amplification gene with ERBB2amp (p＜0.01). FGFR3 mutations were significantly enriched in ERBB2mut than ERBB2amp (p=0.04). Patients with ERBB2 GAs were significantly more likely to have high tumor mutational burden (p＜0.01).
Conclusions
The study provided the landscape of ERBB2 alterations in UC that may benefit from anti-HER2 agents. Consideration should be given to developing trials inclusive of patients with UC harboring ERBB2 alterations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
143P - Ablation combined with tislelizumab in treating hepatocellular carcinoma: A phase II trial
Presenter: Yangxun Pan
Session: Poster Display
Resources:
Abstract
144P - Integrated clinical and genomic models using machine-learning methods to predict the efficacy of paclitaxel-based chemotherapy in patients with advanced gastric cancer from K-MASTER project
Presenter: Jwa Hoon Kim
Session: Poster Display
Resources:
Abstract
145P - Tislelizumab (TIS) + chemotherapy (Chemo)/chemoradiotherapy (CRT) as neoadjuvant treatment for resectable esophageal squamous cell carcinoma (R-ESCC)
Presenter: Longqi Chen
Session: Poster Display
Resources:
Abstract
146P - Phase (ph) Ib results of bemarituzumab (BEMA) added to capecitabine/oxaliplatin (CAPOX) or S-1/oxaliplatin (SOX) with or without nivolumab (NIVO) for previously untreated advanced gastric/gastroesophageal junction cancer (G/GEJC): FORTITUDE-103 study
Presenter: Keun-Wook Lee
Session: Poster Display
Resources:
Abstract
147P - Four-year overall survival (OS) update from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma (uHCC)
Presenter: Stephen Chan
Session: Poster Display
Resources:
Abstract
148P - Safety and efficacy of atezolizumab (Atezo) + bevacizumab (Bev) in Japanese patients (pts) with unresectable hepatocellular carcinoma (uHCC): Preliminary analysis of a prospective, multicenter, observational study (ELIXIR)
Presenter: Teiji Kuzuya
Session: Poster Display
Resources:
Abstract
149P - A prospective observational study of MSI screening in unresectable chemotherapy-naïve advanced gastric cancer/gastroesophageal junction cancer: WJOG13320GPS
Presenter: Yukiya Narita
Session: Poster Display
Resources:
Abstract
150P - Anlotinib plus chemotherapy as first-line therapy for gastrointestinal tumor patients with unresectable liver metastasis: Updated results from a multi-cohort, multi-center phase II trial ALTER-G-001-cohort C
Presenter: Junwei Wu
Session: Poster Display
Resources:
Abstract
151P - Relationship between depth of response and early tumor shrinkage with overall survival in advanced pancreatic cancer
Presenter: EMIKA KUROKI
Session: Poster Display
Resources:
Abstract
152P - Interim analysis of the NAPOLEON-2 study: Safety evaluation of nanoliposomal irinotecan with fluorouracil and folinic acid for unresectable pancreatic cancer patients with prior biliary drainage
Presenter: Futa Koga
Session: Poster Display
Resources:
Abstract