Multicentre randomised phase II trial of gemcitabine+platinum, with or without trastuzumab, in advanced or metastatic urothelial carcinoma overexpressing Her2

Oudard, Stéphane; Culine, Stéphane; Vano, Yann; Goldwasser, François; Théodore, Christine; Nguyen, Thierry; Voog, Éric; Banu, E.; Vieillefond, Annick; Priou, Franck; Deplanque, Gaël; Gravis, Gwénaëlle; Ravaud, Alain; Vannetzel, J.M.; Machiels, Jean‐Pascal; Muracciole, Xavier; Pichon, M.; Bay, Jacques‐Olivier; Elaidi, Réza; Teghom, Corine; Radvanyi, François; Beuzeboc, Philippe

doi:10.1016/j.ejca.2014.10.009

Cited by 134 publications

(85 citation statements)

References 26 publications

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“…This includes, for example, the presence of truncated HER2 isoforms lacking the binding region for trastuzumab, activating HER2 mutations that maintain downstream signaling despite extracellular HER2 inhibition or induction of alternative oncogenic pathways such as PI3K or MET to bypass HER2-dependent signaling (reviewed in [10]). In UC, neither the expression of alternative HER2 isoforms nor the spectrum of prevalent HER2 mutations are well defined and may explain the apparent failure in the Oudard trial [8]. Our presented case, however, demonstrates that HER2 targeting is a potentially powerful weapon in a subset of patients with metastatic UC but the treatment may have to be tailored more closely to the individual molecular setting.…”

Section: Discussionmentioning

confidence: 80%

“…Previous reports have demonstrated that HER2 expression in UC correlates with aggressive disease and poor survival rates [5,6]. However, the two currently existing clinical phase II trials assessing the efficacy of trastuzumab-enhanced treatment in HER2-positive UC yielded rather inconclusive outcomes [7,8]. Hussain et al [7] investigated a new combination of trastuzumab with carboplatin, paclitaxel and gemcitabine in 44 HER2-positive patients.…”

Section: Discussionmentioning

confidence: 99%

“…No updated survival data have been reported yet. In a recently published randomized phase II multicenter trial, Oudard et al [8] investigated platinum-based chemotherapy with or without trastuzumab in HER2-positive UC. In a cohort of 563 patients, the authors identified 75 (13.3%) HER2-positive (IHC 2+/3+ and FISH+) primary tumors and finally included 61 patients in the study.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, there was no significant difference between the two treatment arms regarding response and overall survival rates (15.7 months without trastuzumab vs. 14.1 months with trastuzumab). Although the true benefit of trastuzumab might be masked by the simultaneous addition of first-line cytotoxic agents, the Oudard trial [8] suggests that current diagnostic work up might be insufficient for selecting the right patient. Discrepancies exist regarding the rates of HER2-positive patients between different reports although standardized IHC tests are available [5].…”

Section: Discussionmentioning

confidence: 99%

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Complete and Durable Remission of Human Epidermal Growth Factor Receptor 2-Positive Metastatic Urothelial Carcinoma Following Third-Line Treatment with Trastuzumab and Gemcitabine

Wezel

Erben²,

Gaiser³

et al. 2016

Urol Int

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Urothelial carcinoma (UC) is one of the most common cancers and survival rates are low in metastatic disease with currently established first-line platinum-based chemotherapies. Unlike in many other cancers, no clinically established molecular targeted therapies exist for the treatment of this malignancy. Here we present a case of complete tumor remission following third-line treatment with trastuzumab and gemcitabine in a patient with human epidermal growth factor receptor 2 (HER2)-positive UC after progression under cisplatin and vinflunine chemotherapies. This case shows the potential significance of anti-HER2 therapy in selected patients with molecularly characterized UC. Clinical trials so far show inconclusive outcomes of anti-HER2 therapies in UC, indicating further need for both basic research and clinical studies for the identification of resistance factors and improved patient selection.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Complete and Durable Remission of Human Epidermal Growth Factor Receptor 2-Positive Metastatic Urothelial Carcinoma Following Third-Line Treatment with Trastuzumab and Gemcitabine

Wezel

Erben²,

Gaiser³

et al. 2016

Urol Int

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“…There are numerous studies available, which have used anti-HER-2 drug trastuzumab alone or in combination with other chemotherapeutic agents. 41,42,43 Several phase II and even phase III trials are currently investigating the possible benefit of HER-2 targeted therapies for patients with urothelial carcinoma. But role of this drug in treatment of urothelial carcinoma is not well established.…”

Section: Resultsmentioning

confidence: 99%

Her-2 Oncoprotein Expression in Urothelial Carcinoma

Atri¹,

Rana²,

Gupta³

2017

jemds

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BACKGROUNDLow grade non-muscle invasive transitional cell carcinoma is associated with repeated recurrences and progression to high grade tumour. Non-muscle invasive transitional cell carcinoma is associated with poor oncological outcome. Therefore, this study was undertaken to evaluate the expression of HER-2 oncoprotein in transitional cell carcinoma and further to evaluate whether expression of this oncoprotein has relation with grade of tumour and invasion of muscle.The objective of this study is to evaluate the expression of HER-2 protein in low grade, high grade and muscle invasive transitional cell carcinoma using immunohistochemistry.

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Real‐world effectiveness and safety of RC48‐ADC alone or in combination with PD‐1 inhibitors for patients with locally advanced or metastatic urothelial carcinoma: A multicenter, retrospective clinical study

Xu,

Zhang,

Zhang

et al. 2023

Cancer Medicine

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IntroductionPrevious RC48 (Disitamab Vedotin) studies established that the safety and efficacy of RC48‐antibody–drug conjugate (ADC), either alone or combined with toripalimab, for metastatic urothelial carcinoma (mUC) patients exhibiting human epidermal growth factor receptor 2 (HER2)‐positive or even HER2‐negative status after standard chemotherapy failure.MethodsWith locally advanced or metastatic urothelial carcinoma (la/mUC), patients who received RC48‐ADC monotherapy or a combination with programmed cell death protein 1 (PD‐1) inhibitors between August 2021 and October 2022 were enrolled in this retrospective observational study to evaluate the real‐world antitumor effectiveness and safety.ResultsAmong the 38 enrolled patients (29 males; median age 67.5 years [38–93]), 8 received RC48‐ADC monotherapy, while 30 received combination therapy. Initially, 63.2% (24/38) of the patients had received ≥1 line of prior treatment, and 63.2% (24/38) had visceral metastasis. UC of the bladder represented the majority type in 68.4% (26/38) of cases. By the data cutoff in March 2023, the overall objective response rate (ORR) was 63.2% (95% CI, 47.1%–79.2%), with a disease control rate (DCR) of 89.5% (95% CI, 79.3%–99.7%). Median follow‐up time was 10.6 months. The median progression‐free survival (PFS) was 8.2 months (95% CI, 5.9–10.5), with a 6‐month PFS rate of 63.2% and a 12‐month PFS rate of 34.1%. Median overall survival (OS) was not reached, with a 12‐month OS rate of 76.7%. The median duration of response was 7.3 months (95% CI, 4.6–10.0) among 24 patients evaluated as partial response (PR). The most common treatment‐related adverse events (TRAEs) included anemia (71.1%), anorexia (57.9%), asthenia (52.6%), hypoesthesia (52.6%), bone marrow suppression (47.4%), alopecia (47.4%), nausea (44.7%), proteinuria (36.8%), vomiting (34.2%), and hypoalbuminemia (31.6%). No patient experienced TRAEs of Grade ≥3. One patient had an immune‐related adverse event (irAE) of rash related to toripalimab.ConclusionsBoth as monotherapy and in combination with PD‐1 inhibitors, RC48‐ADC exhibits promising effectiveness and manageable safety profile for mUC patients in real‐world settings.

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Multicentre randomised phase II trial of gemcitabine+platinum, with or without trastuzumab, in advanced or metastatic urothelial carcinoma overexpressing Her2

Cited by 134 publications

References 26 publications

Complete and Durable Remission of Human Epidermal Growth Factor Receptor 2-Positive Metastatic Urothelial Carcinoma Following Third-Line Treatment with Trastuzumab and Gemcitabine

Complete and Durable Remission of Human Epidermal Growth Factor Receptor 2-Positive Metastatic Urothelial Carcinoma Following Third-Line Treatment with Trastuzumab and Gemcitabine

Her-2 Oncoprotein Expression in Urothelial Carcinoma

Real‐world effectiveness and safety of RC48‐ADC alone or in combination with PD‐1 inhibitors for patients with locally advanced or metastatic urothelial carcinoma: A multicenter, retrospective clinical study

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