Radiation therapy enhances immunotherapy response in microsatellite stable colorectal and pancreatic adenocarcinoma in a phase II trial Journal Article

   

Authors:	Parikh, A. R.; Szabolcs, A.; Allen, J. N.; Clark, J. W.; Wo, J. Y.; Raabe, M.; Thel, H.; Hoyos, D.; Mehta, A.; Arshad, S.; Lieb, D. J.; Drapek, L. C.; Blaszkowsky, L. S.; Giantonio, B. J.; Weekes, C. D.; Zhu, A. X.; Goyal, L.; Nipp, R. D.; Dubois, J. S.; Van Seventer, E. E.; Foreman, B. E.; Matlack, L. E.; Ly, L.; Meurer, J. A.; Hacohen, N.; Ryan, D. P.; Yeap, B. Y.; Corcoran, R. B.; Greenbaum, B. D.; Ting, D. T.; Hong, T. S.
Article Title:	Radiation therapy enhances immunotherapy response in microsatellite stable colorectal and pancreatic adenocarcinoma in a phase II trial
Abstract:	Overcoming intrinsic resistance to immune checkpoint blockade for microsatellite stable (MSS) colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) remains challenging. We conducted a single-arm, non-randomized, phase II trial (NCT03104439) combining radiation, ipilimumab and nivolumab to treat patients with metastatic MSS CRC (n = 40) and PDAC (n = 25) with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. The primary endpoint was disease control rate (DCR) by intention to treat. DCRs were 25% for CRC (ten of 40; 95% confidence interval (CI), 13–41%) and 20% for PDAC (five of 25; 95% CI, 7–41%). In the per-protocol analysis, defined as receipt of radiation, DCR was 37% (ten of 27; 95% CI, 19–58%) in CRC and 29% (five of 17; 95% CI, 10–56%) in PDAC. Pretreatment biopsies revealed low tumor mutational burden for all samples but higher numbers of natural killer (NK) cells and expression of the HERVK repeat RNA in patients with disease control. This study provides proof of concept of combining radiation with immune checkpoint blockade in immunotherapy-resistant cancers. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
Keywords:	immunohistochemistry; adult; clinical article; middle aged; gene mutation; overall survival; fatigue; bevacizumab; fluorouracil; colorectal cancer; phenotype; dna damage; ipilimumab; progression free survival; computer assisted tomography; gene expression; mucosa inflammation; protein p53; irinotecan; monoclonal antibody; lymphocytopenia; immunotherapy; microsatellite instability; pancreas adenocarcinoma; natural killer cell; disease control; oxaliplatin; immunosuppressive treatment; k ras protein; genomic dna; epithelial mesenchymal transition; familial adenomatous polyposis; pancreatic ductal carcinoma; immune checkpoint inhibitor; activated partial thromboplastin time; nivolumab; human; article; rna sequencing; microsatellite stable; mrna expression assay; whole exome sequencing; ecog performance status; bilateral salpingo-oophorectomy
Journal Title:	Nature Cancer
Volume:	2
Issue:	11
ISSN:	2662-1347
Publisher:	Nature Research
Date Published:	2021-11-01
Start Page:	1124
End Page:	1135
Language:	English
DOI:	10.1038/s43018-021-00269-7
PROVIDER:	scopus
PMCID:	PMC8809884
PUBMED:	35122060
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85119449677&doi=10.1038%2fs43018-021-00269-7&partnerID=40&md5=482cc9d0d57242785f16dc4a892043f4
Notes:	Article -- Export Date: 3 January 2022 -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/191769