Advanced search
1 file | 991.61 KB

A phase II trial of stereotactic body radiotherapy with concurrent anti-PD1 treatment in metastatic melanoma : evaluation of clinical and immunologic response

Katrien De Wolf, VIBEKE KRUSE (UGent) , Nora Sundahl (UGent) , Mireille Van Gele (UGent) , INES CHEVOLET (UGent) , Reinhart Speeckaert (UGent) , Lieve Brochez (UGent) and Piet Ost (UGent)
Author
Organization
Abstract
Background: Antibodies blocking programmed cell death 1 (PD-1) have encouraging responses in patients with metastatic melanoma. Response to anti-PD-1 treatment requires pre-existing CD8+ T cells that are negatively regulated by PD-1-mediated adaptive immune resistance. Unfortunately, less than half of melanoma tumours have these characteristics. Combining anti-PD-1 treatment with other immunomodulating treatments to activate CD8+ T cells is therefore of vital importance to increase response rates and long-term survival benefit in melanoma patients. Both preclinical and retrospective clinical data support the hypothesis that radiotherapy increases the response rates to anti-PD-1 treatment by stimulating the accumulation and activation of CD8+ T cells in the tumour microenvironment. Combining radiotherapy with a PD-1 blocking antibody might therefore increase response rates and even induce long-term survival. The current phase II study will be testing these hypotheses and aims to improve local and distant tumour responses by exploiting the pro-immunogenic effects of radiotherapy in addition to anti-PD-1 treatment. Methods: The trial will be conducted in patients with metastatic melanoma. Nivolumab or pembrolizumab, both antibodies that target PD-1, will be administrated according to the recommended dosing schedule. Prior to the 2nd cycle, radiotherapy will be delivered in three fractions of 8 Gy to the largest FDG-avid metastatic lesion. The primary endpoint is the proportion of patients with a partial or complete response in non-irradiated metastases according to RECIST v1.1. Secondary endpoints include response rate according to immune related response criteria, metabolic response, local control and survival. To identify peripheral blood biomarkers, peripheral blood mononuclear cells and serum samples will be collected prospectively before, during and after treatment and subjected to flow cytometry and cytokine measurement. Discussion: The current phase II trial aims at exploring the suggested benefits of combining anti-PD-1 treatment and radiotherapy. The translational focus on immunologic markers might be suitable for predicting efficacy and monitoring the effect so to improve patient selection for future clinical applications.
Keywords
Cancer immunotherapy, Stereotactic body radiotherapy, Metastatic melanoma, Biomarkers, Immune monitoring, LONG-TERM SURVIVAL, RADIATION, TUMORS, GUIDELINES, IMMUNITY, CRITERIA, MICE

Downloads

  • 8525146.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 991.61 KB

Citation

Please use this url to cite or link to this publication:

Chicago
De Wolf, Katrien, VIBEKE KRUSE, Nora Sundahl, Mireille Van Gele, INES CHEVOLET, Reinhart Speeckaert, Lieve Brochez, and Piet Ost. 2017. “A Phase II Trial of Stereotactic Body Radiotherapy with Concurrent anti-PD1 Treatment in Metastatic Melanoma : Evaluation of Clinical and Immunologic Response.” Journal of Translational Medicine 15.
APA
De Wolf, Katrien, KRUSE, V., Sundahl, N., Van Gele, M., CHEVOLET, I., Speeckaert, R., Brochez, L., et al. (2017). A phase II trial of stereotactic body radiotherapy with concurrent anti-PD1 treatment in metastatic melanoma : evaluation of clinical and immunologic response. JOURNAL OF TRANSLATIONAL MEDICINE, 15.
Vancouver
1.
De Wolf K, KRUSE V, Sundahl N, Van Gele M, CHEVOLET I, Speeckaert R, et al. A phase II trial of stereotactic body radiotherapy with concurrent anti-PD1 treatment in metastatic melanoma : evaluation of clinical and immunologic response. JOURNAL OF TRANSLATIONAL MEDICINE. 2017;15.
MLA
De Wolf, Katrien, VIBEKE KRUSE, Nora Sundahl, et al. “A Phase II Trial of Stereotactic Body Radiotherapy with Concurrent anti-PD1 Treatment in Metastatic Melanoma : Evaluation of Clinical and Immunologic Response.” JOURNAL OF TRANSLATIONAL MEDICINE 15 (2017): n. pag. Print.
@article{8506632,
  abstract     = {Background: Antibodies blocking programmed cell death 1 (PD-1) have encouraging responses in patients with metastatic melanoma. Response to anti-PD-1 treatment requires pre-existing CD8+ T cells that are negatively regulated by PD-1-mediated adaptive immune resistance. Unfortunately, less than half of melanoma tumours have these characteristics. Combining anti-PD-1 treatment with other immunomodulating treatments to activate CD8+ T cells is therefore of vital importance to increase response rates and long-term survival benefit in melanoma patients. Both preclinical and retrospective clinical data support the hypothesis that radiotherapy increases the response rates to anti-PD-1 treatment by stimulating the accumulation and activation of CD8+ T cells in the tumour microenvironment. Combining radiotherapy with a PD-1 blocking antibody might therefore increase response rates and even induce long-term survival. The current phase II study will be testing these hypotheses and aims to improve local and distant tumour responses by exploiting the pro-immunogenic effects of radiotherapy in addition to anti-PD-1 treatment. 
Methods: The trial will be conducted in patients with metastatic melanoma. Nivolumab or pembrolizumab, both antibodies that target PD-1, will be administrated according to the recommended dosing schedule. Prior to the 2nd cycle, radiotherapy will be delivered in three fractions of 8 Gy to the largest FDG-avid metastatic lesion. The primary endpoint is the proportion of patients with a partial or complete response in non-irradiated metastases according to RECIST v1.1. Secondary endpoints include response rate according to immune related response criteria, metabolic response, local control and survival. To identify peripheral blood biomarkers, peripheral blood mononuclear cells and serum samples will be collected prospectively before, during and after treatment and subjected to flow cytometry and cytokine measurement. 
Discussion: The current phase II trial aims at exploring the suggested benefits of combining anti-PD-1 treatment and radiotherapy. The translational focus on immunologic markers might be suitable for predicting efficacy and monitoring the effect so to improve patient selection for future clinical applications.},
  articleno    = {21},
  author       = {De Wolf, Katrien and KRUSE, VIBEKE and Sundahl, Nora and Van Gele, Mireille and CHEVOLET, INES and Speeckaert, Reinhart and Brochez, Lieve and Ost, Piet},
  issn         = {1479-5876},
  journal      = {JOURNAL OF TRANSLATIONAL MEDICINE},
  keyword      = {Cancer immunotherapy,Stereotactic body radiotherapy,Metastatic melanoma,Biomarkers,Immune monitoring,LONG-TERM SURVIVAL,RADIATION,TUMORS,GUIDELINES,IMMUNITY,CRITERIA,MICE},
  language     = {eng},
  pages        = {6},
  title        = {A phase II trial of stereotactic body radiotherapy with concurrent anti-PD1 treatment in metastatic melanoma : evaluation of clinical and immunologic response},
  url          = {http://dx.doi.org/10.1186/s12967-017-1123-x},
  volume       = {15},
  year         = {2017},
}

Altmetric
View in Altmetric
Web of Science
Times cited: