HER2-Positive Urothelial Carcinoma: Current Evidence on Targeted Agents and Immunotherapy-Based Combinations

Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229–63.

Article  PubMed  Google Scholar 

National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer stat facts: bladder cancer. https://seer.cancer.gov/statfacts/html/urinb.html. Accessed 5 Nov 2023.

Flaig TW, Spiess PE, Abern M, et al. NCCN Guidelines® insights: bladder cancer, version 3.2024. J Natl Compr Canc Netw. 2024;22(4):216–25.

Article  CAS  PubMed  Google Scholar 

Powles T, Bellmunt J, Comperat E, ESMO Guidelines Committee, et al. ESMO clinical practice guideline interim update on first-line therapy in advanced urothelial carcinoma. Ann Oncol. 2024;35(6):485–90.

Article  CAS  PubMed  Google Scholar 

Powles T, Valderrama BP, Gupta S, et al. Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer. N Engl J Med. 2024;390(10):875–88.

Article  CAS  PubMed  Google Scholar 

van der Heijden MS, Sonpavde G, Powles T, et al. Nivolumab plus gemcitabine–cisplatin in advanced urothelial carcinoma. N Engl J Med. 2023;389(19):1778–89.

Article  PubMed  Google Scholar 

Powles T, Park SH, Caserta C, et al. Avelumab first-line maintenance for advanced urothelial carcinoma: results from the JAVELIN Bladder 100 trial after ≥2 years of follow-up. J Clin Oncol. 2023;41(19):3486–92.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Fradet Y, Bellmunt J, Vaughn DJ, et al. Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up. Ann Oncol. 2019;30(6):970–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Loriot Y, Matsubara N, Park SH, THOR Cohort 1 Investigators, et al. Erdafitinib or chemotherapy in advanced or metastatic urothelial carcinoma. N Engl J Med. 2023;389(21):1961–71.

Article  CAS  PubMed  Google Scholar 

Swami U, Grivas P, Pal SK, et al. Utilization of systemic therapy for treatment of advanced urothelial carcinoma: lessons from real world experience. Cancer Treat Res Commun. 2021;27: 100325.

Article  PubMed  Google Scholar 

Marín ÁP, Arranz EE, Sánchez AR, et al. Role of anti-HER2 therapy in bladder carcinoma. J Cancer Res Clin Oncol. 2010;136(12):1915–20.

Article  PubMed  Google Scholar 

Moasser MM. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene. 2007;26(45):6469–87.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wolff AC, Hammond MEH, Allison KH, et al. Human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Focused Update. J Clin Oncol. 2018;36(20):2105–22.

Article  CAS  PubMed  Google Scholar 

Cocco E, Lopez S, Santin AD, et al. Prevalence and role of HER2 mutations in cancer. Pharmacol Ther. 2019;199:188–96.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Koshkin VS, Boyiddle C, Schwartz N, et al. Systematic literature review and testing of HER2 status in urothelial carcinoma (UC). J Clin Oncol. 2023;41(6_suppl):556.

Article  Google Scholar 

Zhao J, Xu W, Zhang Z, et al. Prognostic role of HER2 expression in bladder cancer: a systematic review and meta-analysis. Int Urol Nephrol. 2015;47(1):87–94.

Article  CAS  PubMed  Google Scholar 

Fleischmann A, Rotzer D, Seiler R, et al. Her2 amplification is significantly more frequent in lymph node metastases from urothelial bladder cancer than in the primary tumours. Eur Urol. 2011;60(2):350–7.

Article  CAS  PubMed  Google Scholar 

Chu CE, De Jesus Escano M, Yip W, et al. Human epidermal growth factor receptor 2 (HER2) and fibroblast growth factor receptor 3 (FGFR3) mutations to reveal biological pathways in urothelial carcinoma. J Clin Oncol. 2022;40(6_suppl):567.

Article  Google Scholar 

Zhou Q, Jin P, Liu J, et al. HER2 overexpression triggers the IL-8 to promote arsenic-induced EMT and stem cell-like phenotypes in human bladder epithelial cells. Ecotoxicol Environ Saf. 2021;208: 111693.

Article  CAS  PubMed  Google Scholar 

Nam W, Chae HK, Jung Y, et al. HER2 positivity predicts BCG unresponsiveness and adaptive immune cell exhaustion in EORTC risk-stratified cohort of bladder cancer. Front Immunol. 2023;14:1301510.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kim D, Kim JM, Kim JS, et al. Differential expression and clinicopathological significance of HER2, indoleamine 2,3-dioxygenase and PD-L1 in urothelial carcinoma of the bladder. J Clin Med. 2020;9(5):1265.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Liu H, Chen J, Liu H, et al. The tumor immune profile of bladder cancer (BC) with HER2 over-expression and the investigation into RC48-ADC versus BCG in high-risk non-muscle invasive BC with HER2 over-expression. J Clin Oncol. 2024;42(16_Suppl):e16614.

Article  Google Scholar 

D’Angelo A, Chapman R, Sirico M, et al. An update on antibody–drug conjugates in urothelial carcinoma: state of the art strategies and what comes next. Cancer Chemother Pharmacol. 2022;90(3):191–205.

Article  PubMed  PubMed Central  Google Scholar 

Junttila TT, Akita RW, Parsons K, et al. Ligand-independent HER2/HER3/PI3K complex is disrupted by trastuzumab and is effectively inhibited by the PI3K inhibitor GDC-0941. Cancer Cell. 2009;15(5):429–40.

Article  CAS  PubMed  Google Scholar 

Hussain MH, MacVicar GR, Petrylak DP, et al. Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu–positive urothelial carcinoma: results of a multicenter phase II National Cancer Institute trial. J Clin Oncol. 2007;25(16):2218–24.

Article  CAS  PubMed  Google Scholar 

Oudard S, Culine S, Vano Y, et al. Multicentre randomised phase II trial of gemcitabine + platinum, with or without trastuzumab, in advanced or metastatic urothelial carcinoma overexpressing Her2. Eur J Cancer. 2015;51(1):45–54.

Article  CAS  PubMed  Google Scholar 

Sweeney CJ, Hainsworth JD, Bose R, et al. MyPathway human epidermal growth factor receptor 2 basket study: pertuzumab + trastuzumab treatment of a tissue-agnostic cohort of patients with human epidermal growth factor receptor 2-altered advanced solid tumors. J Clin Oncol. 2024;42(3):258–65.

Article  CAS  PubMed  Google Scholar 

Galsky MD, Von Hoff DD, Neubauer M, et al. Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors. Invest New Drugs. 2012;30(2):695–701.

Article  CAS  PubMed  Google Scholar 

Wülfing C, Machiels JP, Richel DJ, et al. A single-arm, multicenter, open-label phase 2 study of lapatinib as the second-line treatment of patients with locally advanced or metastatic transitional cell carcinoma. Cancer. 2009;115(13):2881–90.

Article  PubMed  Google Scholar 

Powles T, Huddart RA, Elliott T, et al. Phase III, double-blind, randomized trial that compared maintenance lapatinib versus placebo after first-line chemotherapy in patients with human epidermal growth factor receptor 1/2–positive metastatic bladder cancer. J Clin Oncol. 2016;35(1):48–55.

Article  PubMed  Google Scholar 

Tang S, Dorff TBB, Tsao-Wie DDD, et al. Single arm phase II study of docetaxel and lapatinib in metastatic urothelial cancer: USC trial 4B–10-4. J Clin Oncol. 2016;34(2_suppl):424.

Article  Google Scholar 

Cerbone L, Sternberg CN, Sengeløv L, et al. Results from a phase I study of lapatinib with gemcitabine and cisplatin in advanced or metastatic bladder cancer: EORTC Trial 30061. Oncology. 2015;90(1):21–8.

Article  PubMed  Google Scholar 

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