A phase II trial of durvalumab and tremelimumab in metastatic, non‐urothelial carcinoma of the urinary tract

Sarfaty, Michal; Whiting, Karissa; Teo, Min Yuen; Lee, Chung-Han; Peters, V. V.; Durocher, Jennifer; Regazzi, Ashley Marie; McCoy, Asia S.; Hettich, Grace; Jungbluth, Achim A.; Al‐Ahmadie, Hikmat; Ostrovnaya, Irina; Chaim, Joshua; Bajorin, Dean F.; Rosenberg, Jonathan E.; Iyer, Gopa; Funt, Samuel A.

doi:10.1002/cam4.3699

Cited by 14 publications

(9 citation statements)

References 46 publications

(97 reference statements)

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“…The electronic search identified 267 articles; after exclusion of duplicates, irrelevant articles, reviews, and papers not in English or with missing data, 19 articles were finally included for revision [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]. Figure 1 depicts a flowchart describing the details of the document screening process, while Table 1 reports the principal details of the articles finally selected.…”

Section: Resultsmentioning

confidence: 99%

“…Sarfaty et al performed a study on patients with non-urothelial carcinoma, the smaller counterpart of urologic cancers that includes several histotypes, like squamous cell carcinoma (SCC), adenocarcinoma (ADC), and small cell/neuroendocrine carcinoma (NE) [ 89 ]. In this open-label phase II study, 13 patients (seven NE, three SCC, and three ADC) were treated with durvalumab and tremelimumab [ 31 ]. No significant responses were observed; the median PFS was 1.8 (95% CI 1.25–not reached) months, and the median OS was 6.97 (95% CI 4.34–not reached) months.…”

Section: Discussionmentioning

confidence: 99%

“…Sarfaty et al performed a study on patients with non-urothelial carcinoma, the smaller counterpart of urologic cancers that includes several histotypes, like squamous cell carcinoma (SCC), adenocarcinoma (ADC), and small cell/ neuroendocrine carcinoma (NE) [89]. In this open-label phase II study, 13 patients (seven NE, three SCC, and three ADC) were treated with durvalumab and tremelimumab [31] showed that in durvalumab monotherapy a significant number of patients showed strong disease progression, while combination immunotherapy is a therapeutic option that could be used in selected cases, although predictive biomarkers are lacking.…”

Section: Durvalumab Plus Tremelimumab In Urogenital Tumorsmentioning

confidence: 99%

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Durvalumab Plus Tremelimumab in Solid Tumors: A Systematic Review

et al. 2021

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Introduction: Cancer immunotherapy represents one of the most important innovations in modern medicine. Durvalumab is an anti-programmed cell death ligand 1 (PDL-1) agent which is currently under investigation in several studies in combination with the anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) drug tremelimumab. The aim of this review was to systematically identify and revise the current scientific literature investigating the combination of these two drugs in solid tumors. Methods: A digital search on the Medline (PubMed interface) and Scopus databases for articles published from inception to 26 February 2021 was performed. The terms used for the search were durvalumab AND tremelimumab. Trials reported in English involving adult patients with solid cancers treated with the combination durvalumab plus tremelimumab were retrieved; the references of the articles were cross-checked to identify missing papers. Results: The electronic search produced 267 results; after exclusion of duplicates, irrelevant articles, reviews, and papers not in English or missing data, 19 articles were included for revision. The total number of patients treated with the combination of durvalumab and tremelimumab in the studies retrieved was 2052. Conclusion:The combination of durvalumab plus tremelimumab showed some oncological advantages in comparison with traditional chemotherapies in some subsets of tumors, but generally has not shown consistent advantages in comparison with the employment of durvalumab monotherapy. A number of the studies examined had intrinsic methodological limitations; therefore, future well-designed studies involving larger cohorts are warranted.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…Sarfaty et al performed a study on patients with non-urothelial carcinoma, the smaller counterpart of urologic cancers that includes several histotypes, like squamous cell carcinoma (SCC), adenocarcinoma (ADC), and small cell/ neuroendocrine carcinoma (NE) [89]. In this open-label phase II study, 13 patients (seven NE, three SCC, and three ADC) were treated with durvalumab and tremelimumab [31] showed that in durvalumab monotherapy a significant number of patients showed strong disease progression, while combination immunotherapy is a therapeutic option that could be used in selected cases, although predictive biomarkers are lacking.…”

Section: Durvalumab Plus Tremelimumab In Urogenital Tumorsmentioning

confidence: 99%

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Durvalumab Plus Tremelimumab in Solid Tumors: A Systematic Review

et al. 2021

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“…This report sparked interest among researchers in using immunotherapy to treat SCBC. Durvalumab and tremelimumab were evaluated in metastatic, non-urothelial cancer of the genitourinary tract in a phase II trial [ 9 ]. Seven patients with pure or mixed urothelial/small-cell cancer were included.…”

Section: Discussionmentioning

confidence: 99%

An Unexpected and Unpredictable Emergence of Muscle-Invasive Bladder Cancer in a Patient Successfully Treated With Nivolumab for Small-Cell Bladder Cancer

Guimarães¹,

Pinheiro²,

Pimentel³

et al. 2022

Cureus

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Small-cell bladder cancer (SCBC) is a rare subtype of bladder cancer with aggressive behavior and poor prognosis. Here, we report the case of a 50-year-old man who presented with hematuria for one month. A computed tomography scan showed an exophytic lesion on the right posterolateral wall of the bladder and a single liver metastasis with a 14 mm diameter. Transurethral resection of the bladder tumor was performed, and postoperative examination of the specimen showed muscle-invasive SCBC. Initially, the patient was treated with neoadjuvant chemotherapy. Rapid clinical and imaging deterioration was observed after the premature end of cisplatin and etoposide therapy. Second-line therapy with nivolumab demonstrated systemic and local complete response. However, the patient was further diagnosed with unpredictable and unexpected urothelial muscle-invasive bladder cancer. After 76 months of regular follow-up, imaging workup did not demonstrate SCBC recurrence or urothelial bladder cancer progression. This report highlights this disease’s rarity and severity and no typical or even pathognomonic clinical and radiological presentation. Therefore, histopathology and immunohistochemistry findings play a key role in diagnosis. Immunotherapy has opened a new window in cancer treatment and maybe SCBC patients can benefit from it.

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“…25 The combination of 2 ICI agents results in higher incidence rates of colitis, especially when combining Nivolumab and Ipilimumab or Durvalumab and Tremelimumab. 26,27 The rate of IMDC has also been reported to be higher in patients with underlying melanoma compared with other types of cancer. The etiology of this observation is unknown.…”

Section: Epidemiologymentioning

confidence: 99%

Immunotherapy-induced Colitis

Vaziri¹,

Turshudzhyan

Vecchio³

2022

Journal of Clinical Gastroenterology

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Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of a variety of malignancies including advanced melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancers among others. Since their introduction, there has been significant improvement in survival and prognosis in patients with advanced malignancies. Unfortunately, improved outcomes have come at a price of significant immune-related adverse events, with those of the gastrointestinal tract being the most common. Gastrointestinal immune-related adverse events frequently present as diarrhea and colitis, the severity of which can range from mild diarrhea to fulminant colitis with intestinal perforation. Currently, management of ICI-induced colitis is primarily guided by retrospective studies and expert opinion. A significant number of ICIinduced colitis responds to high-dose corticosteroids; however, some patients require further therapy with biologics. There is limited information on the factors which may predispose patients to ICIinduced colitis. Future research elucidating these risk factors along with development of a scoring system could allow for risk-stratification of patients before initiation of ICI therapy. Such a system may help clinicians and patients keep a high index of suspicion regarding ICI-induced colitis and could hopefully reduce the incidence of severe cases. Similarly, future studies should investigate protective factors against ICI-induced colitis, which could potentially allow more patients to safely benefit from ICI therapy.

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A phase II trial of durvalumab and tremelimumab in metastatic, non‐urothelial carcinoma of the urinary tract

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 14 publications

References 46 publications

Durvalumab Plus Tremelimumab in Solid Tumors: A Systematic Review

Durvalumab Plus Tremelimumab in Solid Tumors: A Systematic Review

An Unexpected and Unpredictable Emergence of Muscle-Invasive Bladder Cancer in a Patient Successfully Treated With Nivolumab for Small-Cell Bladder Cancer

Immunotherapy-induced Colitis

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