| Literature DB >> 35122060 |
Aparna R Parikh1,2, Annamaria Szabolcs2, Jill N Allen1,2, Jeffrey W Clark1,2, Jennifer Y Wo3, Michael Raabe2, Hannah Thel2, David Hoyos4, Arnav Mehta2,5, Sanya Arshad2, David J Lieb5, Lorraine C Drapek1,2, Lawrence S Blaszkowsky1,2, Bruce J Giantonio1,2, Colin D Weekes1,2, Andrew X Zhu1,2, Lipika Goyal1,2, Ryan D Nipp1,2, Jon S Dubois1,2, Emily E Van Seventer2, Bronwen E Foreman2, Lauren E Matlack2, Leilana Ly2, Jessica A Meurer1,2, Nir Hacohen2,5, David P Ryan1,2, Beow Y Yeap1,2, Ryan B Corcoran1,2, Benjamin D Greenbaum4, David T Ting6,7, Theodore S Hong8.
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.Entities:
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Year: 2021 PMID： 35122060 PMCID： PMC8809884 DOI： 10.1038/s43018-021-00269-7
Source DB: PubMed Journal: Nat Cancer ISSN： 2662-1347