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Optimizing Sequence of PD-L1 Immune-Checkpoint Inhibitors and Radiation Therapy in Bladder Cancer

Authors :
Jia Min Huang
Rodrigo Skowronski
Surashri Shinde-Jadhav
Jose Joao Mansure
Ronald Kool
Wassim Kassouf
Mina Ayoub
Gautier Marcq
Côme Tholomier
Fadi Brimo
Source :
Bladder Cancer. 6:295-302
Publication Year :
2020
Publisher :
IOS Press, 2020.

Abstract

BACKGROUND: New bladder preserving strategies are needed for muscle invasive bladder cancer (MIBC). Combined therapy of immune-checkpoint inhibitors and radiation was shown to have synergistic antitumoral effects in preclinical studies. OBJECTIVES: We aim to evaluate whether the sequence of administration of this combined therapy impacts antitumoral response. METHODS: We developed an in-vivo syngeneic MIBC mouse model where murine bladder cancer cells (MB49) were injected subcutaneously in the right flank of C57BL/6 mice. Mice were then randomized to the following treatments: control, anti-programmed cell death ligand 1 (PD-L1) alone, radiation alone (XRT) consisting of 6.25 Gy x2 fractions, concurrent anti-PD-L1 with XRT, neoadjuvant anti-PD-L1 followed by XRT, or XRT followed by adjuvant anti-PD-L1 therapy. Tumor growth, survival, and rate of response were analyzed. RESULTS: Total of 60 mice were randomized. One-way analysis of variance showed statistically significant difference in tumor growth rate across the treatment arms (p = 0.029). Importantly, timing of immunotherapy (neoadjuvant, concurrent, or adjuvant) did not alter either tumor growth or survival (p > 0.05). The rate of response was also similar in each combination arm (p > 0.05). CONCLUSION: Combining anti-PD-L1 immunotherapy and radiation therapy offers optimal antitumoral responses. Timing of immunotherapy (neoadjuvant, concurrent, or adjuvant) does not appear to affect outcomes. Whether the toxicity profile differs across various sequential deliveries of combination therapy requires further evaluation.

Details

ISSN :
23523735 and 23523727
Volume :
6
Database :
OpenAIRE
Journal :
Bladder Cancer
Accession number :
edsair.doi...........b47202b4e21d650c7b69803bba4d524d
Full Text :
https://doi.org/10.3233/blc-200315