Proof-of-principle Phase I results of combining nivolumab with brachytherapy and external beam radiation therapy for Grade Group 5 prostate cancer: safety, feasibility, and exploratory analysis

Yuan, Zhigang; Fernandez, Daniel C.; Dhillon, Jasreman; Abraham-Miranda, Julieta; Awasthi, Shivanshu; Kim, Young‐Chul; Zhang, Jingsong; Jain, Rohit; Serna, Amparo; Pow‐Sang, Julio M.; Poch, Michael; Li, Roger; Manley, Brandon; Fink, Angelina; Naghavi, A.O.; Torres-Roca, Javier F.; Grass, G. Daniel; Kim, Sungjune; Latifi, Kujtim; Hunt, David E.; Johnstone, Peter A.S.; Yamoah, Kosj

doi:10.1038/s41391-020-0254-y

Cited by 21 publications

(15 citation statements)

References 37 publications

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“…Recently, research into tumor immunity has become the most rapidly advancing area within cancer. Immunotherapy provides the unprecedented opportunity to effectively treat malignancies owing to the essential involvement of the immune system in tumor development, progression, and therapy [ 9 ], especially in some malignancies such as hepatocellular carcinoma [ 10 ], early-stage squamous cell cancer of the anal canal [ 11 ], prostate cancer [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Immune-related lncRNAs as predictors of survival in breast cancer: a prognostic signature

Zhao

et al. 2020

J Transl Med

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Background Breast cancer is a highly heterogeneous disease, this poses challenges for classification and management. Long non-coding RNAs play acrucial role in the breast cancersdevelopment and progression, especially in tumor-related immune processes which have become the most rapidly investigated area. Therefore, we aimed at developing an immune-related lncRNA signature to improve the prognosis prediction of breast cancer. Methods We obtained breast cancer patient samples and corresponding clinical data from The Cancer Genome Atlas (TCGA) database. Immune-related lncRNAs were screened by co-expression analysis of immune-related genes which were downloaded from the Immunology Database and Analysis Portal (ImmPort). Clinical patient samples were randomly separated into training and testing sets. In the training set, univariate Cox regression analysis and LASSO regression were utilized to build a prognostic immune-related lncRNA signature. The signature was validated in the training set, testing set, and whole cohorts by the Kaplan–Meier log-rank test, time-dependent ROC curve analysis, principal component analysis, univariate andmultivariate Cox regression analyses. Results A total of 937 immune- related lncRNAs were identified, 15 candidate immune-related lncRNAs were significantly associated with overall survival (OS). Eight of these lncRNAs (OTUD6B-AS1, AL122010.1, AC136475.2, AL161646.1, AC245297.3, LINC00578, LINC01871, AP000442.2) were selected for establishment of the risk prediction model. The OS of patients in the low-risk group was higher than that of patients in the high-risk group (p = 1.215e − 06 in the training set; p = 0.0069 in the validation set; p = 1.233e − 07 in whole cohort). The time-dependent ROC curve analysis revealed that the AUCs for OS in the first, eighth, and tenth year were 0.812, 0.81, and 0.857, respectively, in the training set, 0.615, 0.68, 0.655 in the validation set, and 0.725, 0.742, 0.741 in the total cohort. Multivariate Cox regression analysis indicated the model was a reliable and independent indicator for the prognosis of breast cancer in the training set (HR = 1.432; 95% CI 1.204–1.702, p < 0.001), validation set (HR = 1.162; 95% CI 1.004–1.345, p = 0.044), and whole set (HR = 1.240; 95% CI 1.128–1.362, p < 0.001). GSEA analysis revealed a strong connection between the signature and immune-related biological processes and pathways. Conclusions We constructed and verified a robust signature of 8 immune-related lncRNAs for the prediction of breast cancer patient survival.

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Section: Introductionmentioning

confidence: 99%

Immune-related lncRNAs as predictors of survival in breast cancer: a prognostic signature

Zhao

et al. 2020

J Transl Med

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“…Early phase clinical trials showed that the combination of any kind of immunotherapy with radiotherapy to the prostate or to metastases was safe. In some patients, the combination showed encouraging results: increased CD8+ T-cell response to prostate antigens ( 127 , 129 ), and high complete response rates ( 131 ). In this sense a benefit was found in phase I in 3 patients, and good tolerance with HDRBT, androgen-deprivation therapy and nivolumab ( 127 ).…”

Section: Hormone Therapy and Immunotherapy In Prostate Cancermentioning

confidence: 99%

“…In some patients, the combination showed encouraging results: increased CD8+ T-cell response to prostate antigens ( 127 , 129 ), and high complete response rates ( 131 ). In this sense a benefit was found in phase I in 3 patients, and good tolerance with HDRBT, androgen-deprivation therapy and nivolumab ( 127 ). Local injection of vaccine to the prostate was specifically able to increase PSA-specific T cells ( 130 , 132 ) but disappointingly did not increase tumor responses in a randomized phase 2 trial ( 133 ).…”

Section: Hormone Therapy and Immunotherapy In Prostate Cancermentioning

confidence: 99%

Interaction Between Modern Radiotherapy and Immunotherapy for Metastatic Prostate Cancer

et al. 2021

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Prostate cancer is the most frequently diagnosed cancer in men and a leading cause of cancer-related death. In recent decades, the development of immunotherapies has resulted in great promise to cure metastatic disease. However, prostate cancer has failed to show any significant response, presumably due to its immunosuppressive microenvironment. There is therefore growing interest in combining immunotherapy with other therapies able to relieve the immunosuppressive microenvironment. Radiation therapy remains the mainstay treatment for prostate cancer patients, is known to exhibit immunomodulatory effects, depending on the dose, and is a potent inducer of immunogenic tumor cell death. Optimal doses of radiotherapy are thus expected to unleash the full potential of immunotherapy, improving primary target destruction with further hope of inducing immune-cell-mediated elimination of metastases at distance from the irradiated site. In this review, we summarize the current knowledge on both the tumor immune microenvironment in prostate cancer and the effects of radiotherapy on it, as well as on the use of immunotherapy. In addition, we discuss the utility to combine immunotherapy and radiotherapy to treat oligometastatic metastatic prostate cancer.

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“…However, subsequent studies have shown that there may be dramatic responses to immune checkpoint inhibitors in select populations, in combination with androgen receptor-targeted agents (Carosella et al 2015, Mahoney et al 2015, Graff et al 2016. In a small phase I/II study by Yuan et al, the investigators evaluated the role of nivolumab in combination with ADT and high-dose brachytherapy (HDR) followed by external beam RT and saw that the combination was not only well-tolerated but, on rebiopsy after HDR, 50% of the patients had no residual tumor in four out of six biopsy cores, and there was increased CD8+ and CD4+ T cell infiltration in tumor samples of early responders (Yuan et al 2021). Several clinical trials further investigating the combination of RT and immunotherapy are currently recruiting patients (NCT01436968, NCT01436968, NCT03543189, NCT03795207, NCT01777802) (Table 1).…”

Section: :8mentioning

confidence: 99%

Management of early-stage metastatic prostate cancer: appraisal of locoregional treatments and radiation therapy, with or without immunomodulation

Sandoval

Dohm

Yamoah

2021

Endocrine-Related Cancer

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The current standard for the management of locally advanced and early-stage metastatic prostate cancer relies on a backbone of androgen deprivation therapy (ADT) combined with radiotherapy (RT), a regimen that at a glance appears relatively straightforward. The emergence of newer diagnostic, genomic and imaging modalities have allowed for better disease risk-stratification and opened avenues for the development of more patient-centered treatment strategies. This review aims to highlight the central role of RT as part of a multi-modal approach, and discuss established and emerging data for the management of locally advanced disease, biochemical recurrence, and oligometastatic disease, as well as the use of immunotherapies and radio-isotopes. This review will also briefly discuss ongoing clinical trials that provide new insights into the paradigm shift in the management of locally advanced prostate cancer.

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Proof-of-principle Phase I results of combining nivolumab with brachytherapy and external beam radiation therapy for Grade Group 5 prostate cancer: safety, feasibility, and exploratory analysis

Cited by 21 publications

References 37 publications

Immune-related lncRNAs as predictors of survival in breast cancer: a prognostic signature

Immune-related lncRNAs as predictors of survival in breast cancer: a prognostic signature

Interaction Between Modern Radiotherapy and Immunotherapy for Metastatic Prostate Cancer

Management of early-stage metastatic prostate cancer: appraisal of locoregional treatments and radiation therapy, with or without immunomodulation

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