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  1. Article ; Online: PD-1/PD-L1 Combinations in Advanced Urothelial Cancer: Rationale and Current Clinical Trials.

    Hsu, Miles M / Balar, Arjun V

    Clinical genitourinary cancer

    2019  Volume 17, Issue 3, Page(s) e618–e626

    Abstract: Chemotherapy is no longer the only viable option for patients with locally advanced or metastatic urothelial carcinoma. Immunotherapy, as checkpoint inhibition, has received United States Food and Drug Administration approval in the preceding several ... ...

    Abstract Chemotherapy is no longer the only viable option for patients with locally advanced or metastatic urothelial carcinoma. Immunotherapy, as checkpoint inhibition, has received United States Food and Drug Administration approval in the preceding several years, both in the second-line and first-line for cisplatin-ineligible patients. Those who respond often do so durably; however, response rates in the first line are 23% to 24%, and are lower in the second line. With a focus on urothelial carcinoma, this review discusses the tumor microenvironment and its negative influence on anti-tumor immunity, as well as measures to counteract immune suppression or evasion. The review then describes a range of current clinical trials implementing these measures in the form of programmed death-combination therapy, specifically in advanced bladder and urothelial cancers.
    MeSH term(s) Antineoplastic Agents, Immunological/pharmacology ; Antineoplastic Agents, Immunological/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; B7-H1 Antigen/antagonists & inhibitors ; Carcinoma, Transitional Cell/drug therapy ; Carcinoma, Transitional Cell/immunology ; Clinical Trials as Topic ; Humans ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Survival Analysis ; Treatment Outcome ; Tumor Microenvironment/drug effects ; Urologic Neoplasms/drug therapy ; Urologic Neoplasms/immunology
    Chemical Substances Antineoplastic Agents, Immunological ; B7-H1 Antigen ; CD274 protein, human ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor
    Language English
    Publishing date 2019-03-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2225121-2
    ISSN 1938-0682 ; 1558-7673
    ISSN (online) 1938-0682
    ISSN 1558-7673
    DOI 10.1016/j.clgc.2019.03.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6168: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Outcomes With First-line PD-1/PD-L1 Inhibition in Advanced Urothelial Cancer: A Single Institution Experience.

    Hsu, Miles M / Xia, Yuhe / Troxel, Andrea / Delbeau, Daniela / Francese, Kaitlyn / Leis, Dayna / Shepherd, Deneuve / Balar, Arjun V

    Clinical genitourinary cancer

    2019  Volume 18, Issue 3, Page(s) e209–e216

    Abstract: Background: First-line PD-inhibition in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer represents a novel clinical setting, with uncertainty concerning second-line outcomes. Specifying second-line treatment and ... ...

    Abstract Background: First-line PD-inhibition in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer represents a novel clinical setting, with uncertainty concerning second-line outcomes. Specifying second-line treatment and outcomes will provide guidance in this new sequence. We performed a retrospective chart review to document the outcomes of these patients treated at our institution.
    Patients and methods: Our cohort consisted of 43 patients with advanced urothelial cancer receiving first-line checkpoint inhibition. Baseline factors, programmed death-ligand 1 (PD-L1) status, treatments, and outcomes during and beyond the first line were obtained. Response was scored using Response Evaluation Criteria in Solid Tumors, version 1.1 criteria. Log rank tests were used to compare outcomes in prognostic subgroups, and outcome associations with PD-L1 status were analyzed with Fisher exact tests.
    Results: A total of 43 patients received first-line atezolizumab or pembrolizumab from June 2014 until June 2018. The median age was 76.8 years, and the population was 74% male, with 60% having visceral metastases. Reasons for cisplatin ineligibility were Eastern Cooperative Oncology Group performance status 2%, 30%; renal insufficiency, 44%, and both, 21%. First-line objective response rate (ORR) was 30%, and complete response was 14%. The median overall survival was 11.7 months. Of 29 patients progressing, 17 received second-line treatment (most commonly, gemcitabine/carboplatin [10 patients]). The second-line response rate was 33%, and the ORR was 11%. The second-line median overall survival was 6.2 months. No association was found between PD-L1 status and outcomes.
    Conclusion: Outcomes with first-line immunotherapy are consistent with historical outcomes. The ORR after first-line checkpoint inhibition falls short of historical comparators; however, the response rate compares favorably to those of chemotherapies used in previous second-line regimens. The older age and poorer performance status may have contributed to second-line outcomes.
    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; B7-H1 Antigen/antagonists & inhibitors ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prognosis ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Response Evaluation Criteria in Solid Tumors ; Retrospective Studies ; Survival Rate ; Urologic Neoplasms/drug therapy ; Urologic Neoplasms/immunology ; Urologic Neoplasms/pathology
    Chemical Substances Antibodies, Monoclonal, Humanized ; B7-H1 Antigen ; CD274 protein, human ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor ; atezolizumab (52CMI0WC3Y) ; pembrolizumab (DPT0O3T46P)
    Language English
    Publishing date 2019-10-16
    Publishing country United States
    Document type Clinical Trial ; Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2225121-2
    ISSN 1938-0682 ; 1558-7673
    ISSN (online) 1938-0682
    ISSN 1558-7673
    DOI 10.1016/j.clgc.2019.10.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 6168: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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