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A Human Peripheral Blood Mononuclear Cell PBMC Engrafted Humanized Xenograft Model for Translational Immuno-oncology I-O Research
Published on: August 15, 2019
[Immunooncology in Urologic Cancers: Current Status]
1Urologische Klinik und Poliklinik, Universitätsklinikum Jena, Jena.
Abstract:
Immune checkpoint inhibitors are establishing itselves as a new systemic treatment option (in addition to chemotherapy and targeted therapy) for metastatic tumours. (Re)activating the immune system, these antibodies may lead to impressive remissions lasting for a long time in some patients. Regarding urological tumours, the anti-PD-1 antibody Nivolumab (Opdivo(®)) has been approved this year for advanced, previously treated renal cell carcinoma. In the United States, Atezolizumab (Tecentriq(®)) has been approved for metastatic urothelial carcinoma after platinum-based chemotherapy. In patients pre-treated with antiangiogenic drugs, Nivolumab has achieved a higher rate of remission (25 vs. 5%) and a 5.4-month increase in overall survival compared with Everolimus. An indirect comparison with chemotherapy demonstrates an increased remission rate (15%) and an increased 1-year survival rate (37%) for urothelial carcinoma after platinum-based chemotherapy with Atezolizumab. The frequency of side-effects resulting from these treatments is comparatively low. However, some patients experience what is called immune-mediated side-effects, which must be recognised and treated in a timely manner. Immune checkpoint inhibitors are being tested in numerous ongoing phase III clinical trials and have the potential to replace current first-line treatment options for metastatic tumours such as urothelial and renal cell carcinoma. These trials are also investigating anti-PD-1/anti-PD-L1 antibodies in combination with CTLA4 immune checkpoint inhibitors or antiangiogenic treatments. Approval trials are also investigating the role of immune checkpoint inhibitors in the adjuvant setting.
Insights
Immune checkpoint inhibitors offer new hope for metastatic cancers. These therapies, like Nivolumab and Atezolizumab, show promising long-term remissions and improved survival in urological tumors with manageable side effects.
Area of Science:
- Oncology
- Immunotherapy
Background:
- Immune checkpoint inhibitors (ICIs) represent a novel systemic treatment modality for metastatic tumors.
- These therapies activate the immune system, potentially leading to durable patient remissions.
Purpose of the Study:
- To review the current status and potential of ICIs in treating urological malignancies.
- To highlight approved ICIs and ongoing clinical trials in advanced renal cell and urothelial carcinoma.
Main Methods:
- Review of recent clinical trial data and regulatory approvals for ICIs in urological cancers.
- Comparison of ICI efficacy (response rates, overall survival) against existing treatments like chemotherapy, targeted therapy, and antiangiogenic drugs.
Main Results:
- Nivolumab (anti-PD-1) approved for advanced renal cell carcinoma; Atezolizumab (anti-PD-L1) approved for metastatic urothelial carcinoma.
- Nivolumab demonstrated superior remission rates (25% vs. 5%) and overall survival increase (5.4 months) versus Everolimus in pre-treated patients.
- Atezolizumab showed increased remission (15%) and 1-year survival (37%) compared to chemotherapy in urothelial carcinoma.
Conclusions:
- ICIs are effective and well-tolerated systemic treatments for metastatic urological tumors.
- Ongoing trials explore ICI combinations and adjuvant settings, with potential to supplant current first-line therapies.
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