scholarly journals Treatment-free Survival after Immune Checkpoint Inhibitor Therapy versus Targeted Therapy for Advanced Renal Cell Carcinoma: 42-Month Results of the CheckMate 214 Trial

2021 ◽  
Author(s):  
Meredith M. Regan ◽  
Opeyemi A. Jegede ◽  
Charlene M. Mantia ◽  
Thomas Powles ◽  
Lillian Werner ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Advanced Renal Cell Carcinoma ◽  
Free Survival ◽  
Checkpoint Inhibitor Therapy

Assessing improvements in metastatic renal cell carcinoma systemic treatments from the pre-cytokine to the immune checkpoint inhibitor eras: a retrospective analysis of real-world data

2020 ◽  
Author(s):  
Hiroki Ishihara ◽  
Toshio Takagi ◽  
Tsunenori Kondo ◽  
Hironori Fukuda ◽  
Hidekazu Tachibana ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Molecular Targeted Therapy ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor

Abstract Objective Studies assessing outcome improvements over a long period according to systemic therapy strategies for metastatic renal cell carcinoma using real-world data, including the results of the recent era of immune checkpoint inhibitors, are limited. Herein, we retrospectively evaluated patients who were diagnosed with metastatic renal cell carcinoma over a 40-year span. Methods Patients were classified into four groups based on when their metastases were diagnosed as follows: (i) the pre-cytokine era (1980–1986), (ii) the cytokine era (1987–2007), (iii) the molecular-targeted therapy (mTT) era (2008 to August 2016) and (iv) the immune checkpoint inhibitor era (September 2016 to 2018). The immune checkpoint inhibitor era consisted of second- or later-line nivolumab. Overall survival from the diagnoses of metastases was evaluated. Results In total, 576 patients were evaluated, including 22 (3.82%), 231 (40.1%), 253 (43.9%) and 70 (12.2%) patients from the pre-cytokine, cytokine, molecular-targeted therapy and immune checkpoint inhibitor eras, respectively. The overall survival significantly improved with each successive era (median: 13.1 vs. 24.5 vs. 44.4 months vs. not reached in pre-cytokine vs. cytokine vs. molecular-targeted therapy vs. immune checkpoint inhibitor eras, P < 0.0001). The implementation of molecular-targeted therapy improved overall survival compared with that of cytokine (cytokine vs. molecular-targeted therapy eras, P < 0.0001). Multivariate analysis demonstrated that the era was an independent factor for overall survival (P < 0.0001), together with histopathological type; metastasis status (i.e. synchronous or metachronous); systemic therapy status (i.e. absence or presence) and bone, liver or lymph node metastasis status (all, P < 0.05). Conclusion This retrospective study of real-world data indicated that metastatic renal cell carcinoma outcomes improved with successive systemic therapy paradigms.

First-Line Immunotherapy Combinations in Advanced Renal Cell Carcinoma – A Rapid Review and Meta-Analysis

Kidney Cancer ◽  
2021 ◽  
pp. 1-11
Author(s):  
Jason Shpilsky ◽  
Paul J. Catalano ◽  
David F. McDermott
Keyword(s):  
Renal Cell Carcinoma ◽  
Combination Therapy ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Advanced Renal Cell Carcinoma

Background: Combination or multi-agent therapy including immune checkpoint inhibitors has shifted the landscape of the treatment of advanced/metastatic renal cell carcinoma. There are several approved immune checkpoint inhibitor (ICI) combinations featuring antibodies against programmed cell death protein 1 (PD-1) receptor or its ligand 1 (PD-L1) combined with other immune checkpoint inhibitors, multi-targeted tyrosine kinase inhibitors (TKIs), or other agents active in renal cell carcinoma. Objective: This study aims to compile the evidence of available first-line combination therapies compared to sunitinib monotherapy in advanced renal cell carcinoma. Methods: A systematic literature search was conducted according to the PRISMA statement to identify all randomized Phase III clinical trial data in previously untreated metastatic renal cell carcinoma featuring an immune checkpoint inhibitor combination compared against sunitinib. A two-stage selection process was utilized to determine eligible studies. Of a total of 124 studies and 94 additional abstracts, 6 studies were considered for final analysis. These studies were evaluated for progression free survival (PFS), overall survival (OS), Grade III or higher adverse events (AEs), objective response rate (ORR), and complete response rate (CRR). Results: 6 studies with 5,121 patients met our search criteria. For OS, ICI combination therapy was favored over sunitinib with an estimated combined hazard ratio of 0.74 (0.67–0.81 95% CI). For PFS, ICI combination therapy was favored over sunitinib with an estimated combined hazard ratio of 0.65 (0.52–0.82, 95% CI). The combination of nivolumab and ipilimumab had the longest duration of response and less incidence of grade III or higher adverse events compared to the combination of anti-PD-1/PD-L1 with TKI. The combination of anti-PD-1/PD-L1 with TKI had higher rates of overall response and longer PFS than the combination of nivolumab/ipilimumab. Conclusions: This meta-analysis supports the recommendation of immune checkpoint inhibitor combination therapy over sunitinib monotherapy for previously untreated advanced renal cell carcinoma by virtue of improved PFS and OS. The choice of which ICI combination therapy to use may be guided by patient-specific characteristics including IMDC risk status, adverse effect profile, and need for early response.

scholarly journals Clinical Validation of PBRM1 Alterations as a Marker of Immune Checkpoint Inhibitor Response in Renal Cell Carcinoma

JAMA Oncology ◽  
2019 ◽  
Vol 5 (11) ◽  
pp. 1631 ◽  
Author(s):  
David A. Braun ◽  
Yuko Ishii ◽  
Alice M. Walsh ◽  
Eliezer M. Van Allen ◽  
Catherine J. Wu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Clinical Validation

scholarly journals Current Multimodality Treatments against Brain Metastases from Renal Cell Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2875
Author(s):  
Yoshiyuki Matsui
Keyword(s):  
Renal Cell Carcinoma ◽  
Brain Metastasis ◽  
Cell Carcinoma ◽  
Immune Checkpoint ◽  
Renal Cell ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Target Therapy ◽  
Molecular Target ◽  
Molecular Target Therapy

In patients with renal cell carcinoma, brain metastasis is generally one of the poor prognostic factors. However, the recent introduction of molecular target therapy and immune checkpoint inhibitor has remarkably advanced the systemic treatment of metastatic renal cell carcinoma and prolonged the patients’ survival. The pivotal clinical trials of those agents usually excluded patients with brain metastasis. The incidence of brain metastasis has been increasing in the actual clinical setting because of longer control of extra-cranial disease. Brain metastasis subgroup data from the prospective and retrospective series have been gradually accumulated about the risk classification of brain metastasis and the efficacy and safety of those new agents for brain metastasis. While the local treatment against brain metastasis includes neurosurgery, stereotactic radiosurgery, and conventional whole brain radiation therapy, the technology of stereotactic radiosurgery has been especially advanced, and the combination with systemic therapy such as molecular target therapy and immune checkpoint inhibitor is considered promising. This review summarizes recent progression of multimodality treatment of brain metastasis of renal cell carcinoma from literature data and explores the future direction of the treatment.

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