HER2 overexpression is associated with worse outcomes in patients with upper tract urothelial carcinoma (UTUC)

Soria, Francesco; Moschini, Marco; Haitel, Andrea; Wirth, Grégory J.; Karam, Jose A.; Wood, Christopher G.; Rouprêt, Morgan; Margulis, Vitaly; Karakiewicz, Pierre I.; Briganti, Alberto; Raman, Jay D.; Kammerer‐Jacquet, Solène‐Florence; Mathiéu, Romain; Bensalah, Karim; Lotan, Yair; Özsoy, Mehmet; Remzi, Mesut; Gust, Kilian M.; Shariat, Shahrokh F.

doi:10.1007/s00345-016-1871-x

Cited by 37 publications

(26 citation statements)

References 39 publications

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“…In the largest single-center HER-2 study in UTUC patients ( 32 ), Sasaki et al investigated HER-2 status in 171 UTUC patients who underwent RNU and found that overexpression and amplification of HER-2 was associated with early bladder cancer recurrence. These findings were validated by a large multicenter retrospective study of 732 patients ( 33 ), in which Soria and colleagues found that HER-2 was overexpressed in 35.6% of patients and linked to pathological characteristics, such as more advanced T stage, presence of lymph node metastasis, high-grade tumor, tumor necrosis, and lympho-vascular invasion. By multivariable analysis, HER-2 overexpression remained associated with disease recurrence and overall and cancer-specific mortality.…”

Section: Introductionmentioning

confidence: 82%

Tissue-based molecular markers in upper tract urothelial carcinoma and their prognostic implications

et al. 2018

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Upper tract urothelial carcinoma (UTUC) is a rare and aggressive disease that is associated with high rates of recurrence and death. Radical nephroureterectomy (RNU) with excision of the bladder cuff is considered the standard of care for high-risk UTUC, whereas kidney-sparing techniques can be indicated for select patients with low-risk disease. There is a significant lack of clinical and pathological prognostic factors for stratifying patients with regard to making treatment decisions. Incorporation of tissue-based molecular markers into prognostic tools could help accurately stratify patients for clinical decision-making in this heterogeneous disease. Although the number of studies on tissue-based markers in UTUC has risen dramatically in the past several years—many of which are based on single centers and small cohorts, with a low level of evidence—many discrepancies remain between their results. Nevertheless, certain biomarkers are promising tools, necessitating prospective multi-institution studies to validate their function.

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Section: Introductionmentioning

confidence: 82%

Tissue-based molecular markers in upper tract urothelial carcinoma and their prognostic implications

et al. 2018

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“…A higher incidence rate of UTUC was reported in Asians than western countries, generally about 20-36% in most Asian cohorts with mUC (24).Two phase II trials of two PD-1 antibodies originated in China, toripalimab and tislelizumab, for the treatment of mUC after progression of platinum chemotherapy reported to have 47.2% (25) and 47.0% (26) of mUTUC, respectively, similar to our patient population. 9.4%-41.2% of UBC patients (7,27) and 18.1-35.8% of UTUC (28,29) patients were reported to overexpressed HER2. We did not observe obvious difference in the HER2 expression rate between UTUC and UBC patients in our study (44.1% vs 49.2% in the screened patients).…”

Section: Discussionmentioning

confidence: 99%

Open-label, Multicenter, Phase II Study of RC48-ADC, a HER2-Targeting Antibody–Drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma

Sheng

Yan

Wang

et al. 2021

Clinical Cancer Research

174

129

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Platinum-containing chemotherapy is the standard first-line treatment in metastatic urothelial carcinoma (mUC). After the disease progression on standard first-line chemotherapy, anti-PD-1/PD-L1 therapies have emerged as a second-line option but have yielded low response rates in unselected population. Following breast and gastric cancer, UC is the third most prevalent cancer with HER2 overexpression, indicating a potential utility for HER2-targeting therapy in mUC. However, antibodies and tyrosine kinase inhibitors targeting HER2, have failed to show clinical benefits in metastatic UC. This phase 2 clinical trial assessed RC48-ADC, a novel humanized anti-HER2 antibody conjugated with monomethyl auristatin E (MMAE), in 43 patients with HER2-positive (IHC 3+ and 2+) locally advanced or metastatic UC who progressed on systemic chemotherapy. We observed an objective response rate of 51.2% and progression-free survival of 6.9 months, showing a higher response rate than historic response rates of currently available immunotherapies in the second-line setting. The efficacy observed in this trial is promising for patients with HER2-positive metastatic UC, which remained an unmet clinical need. Research.

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“…Numerous prognostic molecular biomarkers in UTUC have been described ( Table 5 ). These biomarkers are implicated in every steps of tumorigenesis and progression from cell-cycle regulation [mTOR pathway ( 99 )] to cell-proliferation [HER2 ( 91 ), Ki-67 ( 95 - 97 , 113 ), BCAT1 ( 83 ), CDCA5 ( 84 )] and apoptosis [p53 ( 100 )]. Unfortunately, most of them have been described in single-institution cohorts and very few factors beneficiated from external validation.…”

Section: Evidence Synthesismentioning

confidence: 99%

Predictive models and prognostic factors for upper tract urothelial carcinoma: a comprehensive review of the literature

Mbeutcha

Mathiéu

Rouprêt

et al. 2016

Transl. Androl. Urol.

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In the context of customized patient care for upper tract urothelial carcinoma (UTUC), decision-making could be facilitated by risk assessment and prediction tools. The aim of this study was to provide a critical overview of existing predictive models and to review emerging promising prognostic factors for UTUC. A literature search of articles published in English from January 2000 to June 2016 was performed using PubMed. Studies on risk group stratification models and predictive tools in UTUC were selected, together with studies on predictive factors and biomarkers associated with advanced-stage UTUC and oncological outcomes after surgery. Various predictive tools have been described for advanced-stage UTUC assessment, disease recurrence and cancer-specific survival (CSS). Most of these models are based on well-established prognostic factors such as tumor stage, grade and lymph node (LN) metastasis, but some also integrate newly described prognostic factors and biomarkers. These new prediction tools seem to reach a high level of accuracy, but they lack external validation and decision-making analysis. The combinations of patient-, pathology- and surgery-related factors together with novel biomarkers have led to promising predictive tools for oncological outcomes in UTUC. However, external validation of these predictive models is a prerequisite before their introduction into daily practice. New models predicting response to therapy are urgently needed to allow accurate and safe individualized management in this heterogeneous disease.

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HER2 overexpression is associated with worse outcomes in patients with upper tract urothelial carcinoma (UTUC)

Cited by 37 publications

References 39 publications

Tissue-based molecular markers in upper tract urothelial carcinoma and their prognostic implications

Tissue-based molecular markers in upper tract urothelial carcinoma and their prognostic implications

Open-label, Multicenter, Phase II Study of RC48-ADC, a HER2-Targeting Antibody–Drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma

Predictive models and prognostic factors for upper tract urothelial carcinoma: a comprehensive review of the literature

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