American Association for Cancer Research
10780432ccr210163-sup-258947_2_supp_6995678_qq6n2z.xlsx (2.48 MB)

Supplementary Table 3 from Pilot Clinical Trial of Perioperative Durvalumab and Tremelimumab in the Treatment of Resectable Colorectal Cancer Liver Metastases

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posted on 2023-03-31, 22:28 authored by Preeti Kanikarla Marie, Cara Haymaker, Edwin Roger Parra, Young Uk Kim, Rossana Lazcano, Swati Gite, Daniele Lorenzini, Ignacio I. Wistuba, Rebecca S. Slack Tidwell, Xiaofei Song, Wai Chin Foo, Dipen M. Maru, Yun Shin Chun, Andy Futreal, Bryan Kee, David Menter, Luisa Solis, Ching-Wei Tzeng, Christine Parseghian, Kanwal Raghav, Van Morris, Chia-Chi Chang, Robert Jenq, Alda Tam, Chantale Bernatchez, Scott Kopetz, Jean-Nicolas Vauthey, Michael J. Overman

DEG and GSEA gene set analysis post vs pre treatment





University of Texas MD Anderson Cancer Center Moon Shots Program

University of Texas MD Anderson Cancer Center



Despite the prognostic importance of immune infiltrate in colorectal cancer, immunotherapy has demonstrated limited clinical activity in refractory metastatic proficient mismatch-repair (pMMR) colorectal cancer. This study explores combining anti–CTLA-4 and an anti–PD-L1 therapy in the preoperative management of resectable colorectal cancer liver metastases with the intent to improve immune responses in this disease setting. Patients with resectable colorectal cancer liver-only metastases received one dose of tremelimumab and durvalumab preoperatively followed by single-agent durvalumab postoperatively. Primary objectives were to determine feasibility and safety. A total of 24 patients were enrolled between November 2016 and November 2019. Twenty-three patients received treatment [21 pMMR and 2 deficient mismatch-repair (dMMR)] and subsequently 17 (74%; 95% CI: 53%–88%) underwent surgical resection. Grade 3/4 treatment-related immune toxicity and postoperative grade 3/4 toxicity were seen in 5/23 (22%; 95% CI: 10%–44%) and 2/17 (12%; 95% CI: 2%–38%) patients. The median relapse-free survival (RFS) was 9.7 (95% CI: 8.1–17.8) months, and overall survival was 24.5 (95% CI: 16.5–28.4) months. Four patients demonstrated complete pathologic response, two dMMR patients and two POLE mutation patients. Pre- and post-tumor tissue analysis by flow cytometry, immunofluorescence, and RNA sequencing revealed similar levels of T-cell infiltration, but did demonstrate evidence of CD8+ and CD4+ activation posttreatment. An increase in B-cell transcriptome signature and B-cell density was present in posttreatment samples from patients with prolonged RFS. This study demonstrates the safety of neoadjuvant combination tremelimumab and durvalumab prior to colorectal cancer liver resection. Evidence for T- and B-cell activation following this therapy was seen in pMMR metastatic colorectal cancer.

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