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
497P - Sintilimab in combination with anlotinib in advanced NSCLC treated with first-line PD-1 antibodies: An open, single-arm, phase II trial
Presenter: Ying Jin
Session: Poster Display
Resources:
Abstract
498P - Frailty-adjusted life expectancy and survival in older lung cancer patients: A large-scale electronic health-record based study
Presenter: Thao Tu
Session: Poster Display
Resources:
Abstract
499P - Long-term survival and treatment (tx) patterns after first-line (1L) osimertinib in patients (pts) with epidermal growth factor receptor (EGFR) mutation-positive (m) advanced non-small cell lung cancer (NSCLC): Japanese cohort of a global real-world (rw) observational study
Presenter: Daichi Fujimoto
Session: Poster Display
Resources:
Abstract
500P - The effectiveness and safety of durvalumab after chemoradiotherapy for locoregional recurrence of completely resected non-small cell lung cancer: Real-world, multicenter, observational study (NEJ056)
Presenter: Hidehito Horinouchi
Session: Poster Display
Resources:
Abstract
501P - One-year survival outcomes of unresectable stage III non-small cell lung cancer patients who underwent PD-1 inhibitor plus chemo as induction therapy
Presenter: Xin Wang
Session: Poster Display
Resources:
Abstract
502P - Impact of sarcopenia on the outcome of patients with locally advanced non-small cell lung cancer treated with chemoradiotherapy followed by durvalumab
Presenter: Kentaro Tamura
Session: Poster Display
Resources:
Abstract
503P - Clinical outcomes by infusion timing of immune checkpoint inhibitors in patients with locally advanced NSCLC
Presenter: TSUYOSHI HIRATA
Session: Poster Display
Resources:
Abstract
504P - Real-world outcomes with induction systemic therapy for stage III in eligible for upfront local therapy: Pre vs post immunotherapy era in a tertiary referral centre
Presenter: Praveen Kumar Marimuthu
Session: Poster Display
Resources:
Abstract
505P - Neoadjuvant PD-1 inhibitor (tislelizumab) plus platinum–etoposide in patients with limited-stage small cell lung cancer: A phase II trial
Presenter: Junjie Hu
Session: Poster Display
Resources:
Abstract
506P - Intrathoracic progression is still the most dominant failure pattern after first-line chemo-immunotherapy in extensive-stage small-cell lung cancer: Implications for thoracic radiotherapy
Presenter: Byoung Hyuck Kim
Session: Poster Display
Resources:
Abstract