(UroToday.com) The 2026 ASCO annual meeting featured a bladder cancer session and a presentation by Dr. Earle Burgess discussing clinical outcomes with ERBB2 gene amplification and activating mutations in muscle invasive bladder cancer patients treated with neoadjuvant chemotherapy. Cisplatin based neoadjuvant chemotherapy has previously been a therapeutic mainstay for muscle invasive bladder cancer. Activating ERBB2 mutations have been associated with improved pathologic complete response to neoadjuvant chemotherapy in muscle invasive bladder cancer.1 However, the prognostic value of ERBB2 gene amplifications in muscle invasive bladder cancer patients receiving neoadjuvant chemotherapy is not characterized. The impact of ERBB2 gene alterations (mutations + amplifications) on recurrence free survival/overall survival in muscle invasive bladder cancer patients receiving neoadjuvant chemotherapy is also not well defined. Previously, Dr. Burgess and colleagues reported at ASCO GU 2026 that high tumor mutational burden (TMB) is associated with improved clinical outcomes in muscle invasive bladder cancer patients receiving neoadjuvant chemotherapy.2 Given the increased interest in ERBB2 as a therapeutic target in urothelial cancer, Dr. Burgess assessed the impact of ERBB2 gene variants on clinical outcomes in the previously reported cohort.
As previously described,2 the investigators performed genomic analysis on diagnostic TURBT specimens using the Tempus xT platform in a cohort of 91 patients with muscle invasive bladder cancer treated with cisplatin-based neoadjuvant chemotherapy prior to radical cystectomy. Correlation of ERBB2 gene variants with clinical outcomes and TMB was performed using logistic regression, Cox proportional hazards models, and Kaplan-Meier techniques.
ERBB2 gene variants were found in 17 (18.7%) patients and exclusively included 4 (4.4%) mutations and 13 (14.3%) amplifications. All ERBB2 mutations were p.S310F. Pathologic complete response occurred in 3 (75%) patients with mutations and 6 (46.2%) with amplifications. The presence of ERBB2 gene variant (mutations + amplifications) was associated with improved pathologic complete response (OR 3.038, p = 0.048), although ERBB2 gene variants (mutations + amplifications) were not clearly associated with TMB > 10 mutations/Mb (OR 2.217, p = 0.178). Five (29.4%) patients with ERBB2 gene variants relapsed (OR 0.518, p = .288). The median recurrence free survival in patients with and without ERBB2 gene variants was not reached and 54.7 months (HR = 0.50, p = 0.134):
Three (75%) mutations and ten (76.9%) amplifications patients remain alive with a median cohort follow up of 63.6 months. The median overall survival in patients with and without ERBB2 gene variants was not reached and 107.6 months (HR = 0.381, p = 0.098):
Dr. Burgess concluded his presentation discussing clinical outcomes with ERBB2 gene amplification and activating mutations in muscle invasive bladder cancer patients treated with neoadjuvant chemotherapy with the following take home points:
- In muscle invasive bladder cancer patients treated with cisplatin-based neoadjuvant chemotherapy, the presence of ERBB2 gene variants was associated with improved pathologic complete response and showed trends towards improved recurrence free survival and overall survival
- Based on these findings, efforts to characterize the prognostic value of ERBB2 gene variants in contemporary cohorts treated with immune checkpoint inhibitor-based perioperative regimens are underway
Presented by: Earle F. Burgess, MD, Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Charlotte, NC
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the American Society of Clinical Oncology Genitourinary (ASCO) Annual Meeting held in Chicago, IL between May 29th and June 1st, 2026
References:
- Groenendijk FH, de Jong J, van de Putte EEF, et al. ERBB2 Mutations Characterize a Subgroup of Muscle-Invasive Bladder Cancer with Excellent Response to Neoadjuvant Chemotherapy. Eur Urol. 2016;69(3):384-388.
- Burgess et al. Impact of tumor mutational burden on clinical outcomes in muscle-invasive bladder cancer patients treated with neoadjuvant chemotherapy. GU ASCO 2026, abstract 814.