Clinical outcome after progressing to frontline and second-line Anti–PD-1/PD-L1 in advanced urothelial cancer

Lista, Alfonso Gómez De Liaño; Dijk, Nick van; Velasco, Guillermo de; Necchi, Andrea; Lavaud, Pernelle; Morales-Bárrera, Rafael; Gordoa, Teresa Alonso; Maroto, Pablo; Ravaud, Alain; Durán, Ignacio; Szabados, Bernadett; Castellano, Daniel; Giannatempo, Patrizia; Loriot, Yohann; Carles, Joan; Anguera, Geòrgia; Lefort, Félix; Raggi, Daniele; Goupil, Marine Gross; Powles, Thomas; Heijden, Michiel S. van der

doi:10.1016/j.eururo.2019.10.004

Cited by 49 publications

(37 citation statements)

References 27 publications

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“…A substantial number of patients who receive ICIs for aUC (either in first-line or as subsequent/salvage treatment) do not receive subsequent lines of treatment, and this generally portends a poor prognosis [20]. Therefore, if suitability for subsequent treatment after ICIs is limited, it can be useful to have predictive biomarkers to help identify patients most likely to benefit, especially as other novel treatments are approved for aUC.…”

Section: Discussionmentioning

confidence: 99%

A New Prognostic Model in Patients with Advanced Urothelial Carcinoma Treated with First-line Immune Checkpoint Inhibitors

Khaki

Diamantopoulos

et al. 2021

European Urology Oncology

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Section: Discussionmentioning

confidence: 99%

A New Prognostic Model in Patients with Advanced Urothelial Carcinoma Treated with First-line Immune Checkpoint Inhibitors

Khaki

Diamantopoulos

et al. 2021

European Urology Oncology

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“…With a better understanding of CAR-T cells, immune checkpoints and the satisfactory performance of checkpoint blockage, immunotherapy has ascended to the high-profile treatment strategy in the area of cancer research, while increasing numbers of anti-PD-1/PD-L1 drugs, including pembrolizumab and atezolizumab, are successively approved and display clinical efficacy [15][16][17]. Notably, the treatment response rate has been proven to be closely connected with the expression level of PD-1/PD-L1 and other immunerelated biomarkers, and less than half of patients with MIBC show pleasing outcomes following checkpoint blockage [18][19][20]. Therefore, discovering significant…”

Section: Discussionmentioning

confidence: 99%

Establishment of a novel risk score model by comprehensively analyzing the immunogen database of bladder cancer to indicate clinical significance and predict prognosis

Liu

Wang

et al. 2020

Aging

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Background: Bladder cancer (BCa) has the highest incidence of aggressive malignant tumors in the urogenital system and is the ninth most common cancer worldwide. Immune function-related genes (IFRGs), which are plentiful in immune cells and the immune microenvironment (IME), have the potential to assess prognosis and predict the efficacy of immunotherapy. A complete and significant immunogenomic analysis based on abundant BCa genetic samples from The Cancer Genome Atlas (TCGA) will provide insight into the field. Results: A total of 57 differentially expressed IFRGs were significantly associated with the clinical outcomes of patients with BCa. Functional enrichment analysis showed that these genes actively participated in the KEGG pathway of human cytomegalovirus infection. Based on the IFRGs (CALR, MMP9, PAEP, RBP7, STAT1, CACYBP, ANHAK, RAC3, SLIT2, EDNRA, IGF1, NAMPT, NTF3, PPY, ADRB2 and SH3BP2), the risk scores were calculated to predict survival and reveal the relationships with age, sex, grade, staging, T-stage, N-stage, and M-stage. Interestingly, IFRG-based risk scores (IRRSs) reflected the infiltration of several types of immune cells. The expression of CACYBP was more significant in grade 3, T3 and T4 stages than in earlier grades and T-stages. Conclusion: Our results highlighted some sIFRGs with remarkable clinical relevance, showed the driving factors of the immune repertoire, and illustrated the significance of IFRG-based individual immune features in the identification, monitoring, and prognosis of patients with BCa. Methods: Based on the TCGA dataset, we integrated the expression profiles of IFRGs and overall survival (OS) in 430 patients with BCa. Differentially expressed IFRGs and survival-related IFRGs (sIFRGs) were highlighted by calculating the difference algorithm and COX regression analysis in patients with BCa. Based on computational biology, the potential molecular mechanisms and characteristics of these IFRGs were also explored. Using multivariate Cox analysis, new risk scores based on immune-related genes were developed. The expression of CACYBP was verified by qPCR, western blot and immunohistochemistry. The relations between CACYBP and clinical features were proven by immunohistochemistry.

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“…Darüber hinaus stehen in der Drittlinie noch Vinflunin, Paclitaxel oder Docetaxel zur Verfügung. Mit welcher Wirksamkeit der Chemotherapie nach vorangegangener Immuntherapie zu rechnen ist, ist zum aktuellen Zeitpunkt jedoch noch unklar [12,13]. Prinzipiell sind Chemotherapeutika weiterhin wirksam.…”

Section: Aktuell Zugelassene Therapienunclassified

Systemtherapie beim metastasierten Urothelkarzinom − Aktueller Stand und was kommt nach den Checkpointinhibitoren?

2020

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ZusammenfassungDas zunehmende Wissen um den Einfluss des Immunsystems auf Tumorentstehung und -progression haben unser Verständnis von Tumorbiologie in den letzten Jahren grundlegend verändert. Während sich die zur Verfügung stehenden Therapieoptionen für Patienten mit metastasiertem Urothelkarzinom der Harnblase über Jahrzehnte hinweg kaum verbessert haben, hat der Einzug von Immuncheckpoint-Inhibitoren in kurzer Zeit zu einer starken Wandlung der Behandlungslandschaft geführt. Zwar bildet die Cisplatin-basierte Kombinationstherapie auch weiterhin die Hauptsäule, darüber hinaus bestehen aber nun zusätzliche wirkungsvolle Behandlungsoptionen mit den in Europa zugelassenen PD-(L)-1-Inhibitoren Atezolizumab, Pembrolizumab und Nivolumab. Einem bemerkenswerten Langzeitansprechen stehen hier das Auftreten teils schwerster immun-vermittelter Nebenwirkungen sowie eine insgesamt nur geringe Ansprechrate von etwa 25 % gegenüber. Eine Vielzahl aktueller klinischer Studien beschäftigt sich daher besonders mit möglichen Kombinationsansätzen und sinnvollen Therapiesequenzen, um mögliche Synergismen sowie additive Effekte der bisher zur Verfügung stehenden Substanzen unter Berücksichtigung eines vertretbaren Nebenwirkungsprofils optimal auszunutzen. Darüber hinaus werden viele neue Therapieansätze in klinischen Studien erprobt. In diesem Zusammenhang sind besonders die Entwicklungen auf dem Gebiet der Antikörper-Wirkstoff-Konjugate und FGFR-Inhibitoren vor dem Hintergrund der erst kürzlich erfolgten FDA-Zulassung hervorzuheben.Der hier vorliegende Review gibt einen Überblick über die aktuell zur Verfügung stehenden Therapieoptionen im metastasierten Urothelkarzinom der Harnblase und behandelt darüber hinaus schwerpunktmäßig zukünftige Therapieansätze anhand gegenwärtiger Studien.

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Clinical outcome after progressing to frontline and second-line Anti–PD-1/PD-L1 in advanced urothelial cancer

Cited by 49 publications

References 27 publications

A New Prognostic Model in Patients with Advanced Urothelial Carcinoma Treated with First-line Immune Checkpoint Inhibitors

A New Prognostic Model in Patients with Advanced Urothelial Carcinoma Treated with First-line Immune Checkpoint Inhibitors

Establishment of a novel risk score model by comprehensively analyzing the immunogen database of bladder cancer to indicate clinical significance and predict prognosis

Systemtherapie beim metastasierten Urothelkarzinom − Aktueller Stand und was kommt nach den Checkpointinhibitoren?

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