scholarly journals Surgical Safety of Deferred Cytoreductive Nephrectomy Following Pretreatment with Immune Checkpoint Inhibitor–based Dual Combination Therapy

2021 ◽  
Author(s):  
Niels M. Graafland ◽  
Bernadett Szabados ◽  
Chandran Tanabalan ◽  
Teele Kuusk ◽  
Faiz Mumtaz ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Cytoreductive Nephrectomy ◽  
Surgical Safety

scholarly journals Cell-free DNA copy number variations predict efficacy of immune checkpoint inhibitor-based therapy in hepatobiliary cancers

2021 ◽  
Vol 9 (5) ◽  
pp. e001942
Author(s):  
Xu Yang ◽  
Ying Hu ◽  
Keyan Yang ◽  
Dongxu Wang ◽  
Jianzhen Lin ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Clinical Outcome ◽  
Risk Score ◽  
Immune Checkpoint ◽  
Copy Number ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Copy Number Variations ◽  
Risk Scores ◽  
Free Dna

BackgroundThis study was designed to screen potential biomarkers in plasma cell-free DNA (cfDNA) for predicting the clinical outcome of immune checkpoint inhibitor (ICI)-based therapy in advanced hepatobiliary cancers.MethodsThree cohorts including 187 patients with hepatobiliary cancers were recruited from clinical trials at the Peking Union Medical College Hospital. Forty-three patients received combination therapy of programmed cell death protein 1 (PD-1) inhibitor with lenvatinib (ICI cohort 1), 108 patients received ICI-based therapy (ICI cohort 2) and 36 patients received non-ICI therapy (non-ICI cohort). The plasma cfDNA and blood cell DNA mutation profiles were assessed to identify efficacy biomarkers by a cancer gene-targeted next-generation sequencing panel.ResultsBased on the copy number variations (CNVs) in plasma cfDNA, the CNV risk score model was constructed to predict survival by using the least absolute shrinkage and selection operator Cox regression methods. The results of the two independent ICI-based therapy cohorts showed that patients with lower CNV risk scores had longer overall survival (OS) and progression-free survival (PFS) than those with high CNV risk scores (log-rank p<0.01). In the non-ICI cohort, the CNV risk score was not associated with PFS or OS. Furthermore, the results indicated that 53% of patients with low CNV risk scores achieved durable clinical benefit; in contrast, 88% of patients with high CNV risk scores could not benefit from combination therapy (p<0.05).ConclusionsThe CNVs in plasma cfDNA could predict the clinical outcome of the combination therapy of PD-1 inhibitor with lenvatinib and other ICI-based therapies in hepatobiliary cancers.

Association of cytoreductive nephrectomy and survival in the immune checkpoint inhibitor era.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 748-748
Author(s):  
Joseph Miccio ◽  
Sung Jun Ma ◽  
Oluwadamilola Temilade Oladeru ◽  
Daniel X. Yang ◽  
Gabrielle W. Peters ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Cox Regression ◽  
Checkpoint Inhibitor ◽  
Private Insurance ◽  
Cytoreductive Nephrectomy ◽  
Fuhrman Grade ◽  
Cox Regression Analysis ◽  
Academic Center ◽  
Income Insurance

748 Background: Cytoreductive nephrectomy (CN) for patients (pts) with metastatic renal cell carcinoma (mRCC) improved overall survival (OS) in the interferon (IFN) era, but the benefit of CN in the immune checkpoint inhibitor (ICI) era is unknown. Methods: We identified pts with mRCC receiving immunotherapy (IT) from 2004-2015 in the National Cancer Database (NCDB). Pts with partial nephrectomy or ablation were excluded. The ICI era was defined as 2013-2015 based on a high-profile publication in 2012 demonstrating efficacy of ICI in mRCC and the IFN era was defined as 2004-2005 due to FDA approval of sorafenib in 12/2005. Pts receiving CN with TKI were excluded, as prior NCDB study showed an OS benefit to CN in contrast to the results of the CARMENA trial. Univariable (UVA) and multivariable (MVA) associates with OS during each era were identified using Cox regression analysis including age, sex, race, income, insurance, treatment facility type, treatment location, clinical T stage (cT), clinical N stage (cN), histology, Fuhrman grade (FG), other metastectomy, and CN. Results: There was a 65% decline in mRCC pts receiving IT from 2005 to 2006 (end of the IFN era), which remained low (11% rise from 2006-2012) until a 93% rise from 2012 to 2013 (start of the ICI era). 128 of 422 (30.3%) pts in the IFN era received CN compared to 218 of 526 (41.4%) patients in the ICI era, p<0.001. Pts in each era were balanced with respect to median age, race, income, location, cT, and histology, but the ICI era had higher proportions of pts with private insurance, treatment at an academic center, N0 disease, FG 3-4, and other metastatectomy (p<0.05). Most pts with CN in the ICI era had IT after CN (89.9%); this was not coded in the IFN era. In the IFN era, CN compared to IT alone was associated with improved OS on UVA (HR 0.59, 95% CI 0.47-0.73, p<0.001) and MVA (HR 0.62, 95% CI 0.47-0.83, p=0.001). In the ICI era, CN compared to IT alone was associated with improved OS on UVA (HR 0.63, 95% CI 0.49-0.81, p<0.001) but not on MVA (0.82, 95% CI 0.58-1.14, p=0.234). Conclusions: Despite increased utilization of CN for US pts with mRCC treated with IT during the ICI era, the lack of OS benefit in recent years suggests a need for prospective reevaluation of the value CN and its timing with ICI.

Combination Therapy with a Hypomethylating Drug (Decitabine) Plus an Immune Checkpoint Inhibitor (Anti-PD-1H) in the KPC Mouse Model of Pancreatic Cancer

2017 ◽  
Vol 152 (5) ◽  
pp. S42-S43 ◽  
Author(s):  
Tamas A. Gonda ◽  
Benjamin Tycko ◽  
Martha C. Salas ◽  
Catherine Do ◽  
Jarwei Fang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Combination Therapy ◽  
Mouse Model ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor

Combination therapy with immune checkpoint inhibitor and CCK-receptor blockade increases survival in pancreatic cancer

Pancreatology ◽  
2017 ◽  
Vol 17 (4) ◽  
pp. S3-S4
Author(s):  
Jill Smith ◽  
Shangzi Wang ◽  
Sandeep Nadella ◽  
Sandra Jablonski ◽  
Louis Weiner
Keyword(s):  
Pancreatic Cancer ◽  
Combination Therapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Receptor Blockade
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