Immunotherapy in colorectal cancer: Available clinical evidence, challenges and novel approaches
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Immunotherapy in colorectal cancer: Available clinical evidence, challenges and novel approaches. / Tintelnot, Joseph; Stein, Alexander.
in: WORLD J GASTROENTERO, Jahrgang 25, Nr. 29, 07.08.2019, S. 3920-3928.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Review › Forschung
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TY - JOUR
T1 - Immunotherapy in colorectal cancer: Available clinical evidence, challenges and novel approaches
AU - Tintelnot, Joseph
AU - Stein, Alexander
PY - 2019/8/7
Y1 - 2019/8/7
N2 - In contrast to other tumor types, immunotherapy has not yet become a relevant part of the treatment landscape of unselected colorectal cancer. Beside the small subgroup of deficient mismatch repair or microsatellite instable tumors (about 5%) as a surrogate for high mutational burden and subsequently high neoantigen load and immunogenicity, inhibitors of programmed death 1 (PD-1), programmed death ligand 1 (PD-L1) and/or cytotoxic T lymphocyte-associated antigen-4 were not or only modestly effective in metastatic colorectal cancer. Thus, a variety of combination approaches with chemotherapy, targeted therapy, toll-like receptor agonists, local ablation or oncolytic viruses is currently being evaluated in different disease settings. Despite several encouraging single arm data already presented or published, available randomized data are unimpressive. Adding PD-1/PD-L1 inhibitors to fluoropyrimidines and bevacizumab maintenance showed no beneficial impact on delaying progression. In refractory disease, the combination of PD-1/PD-L1 and MEK inhibitor was not different from regorafenib, whereas a PD-1/PD-L1 and cytotoxic T lymphocyte-associated antigen-4 inhibitor combination demonstrated better overall survival compared to supportive care alone. Clinical trials in all disease settings applying different combination approaches are ongoing and may define the role of immunotherapy in colorectal cancer.
AB - In contrast to other tumor types, immunotherapy has not yet become a relevant part of the treatment landscape of unselected colorectal cancer. Beside the small subgroup of deficient mismatch repair or microsatellite instable tumors (about 5%) as a surrogate for high mutational burden and subsequently high neoantigen load and immunogenicity, inhibitors of programmed death 1 (PD-1), programmed death ligand 1 (PD-L1) and/or cytotoxic T lymphocyte-associated antigen-4 were not or only modestly effective in metastatic colorectal cancer. Thus, a variety of combination approaches with chemotherapy, targeted therapy, toll-like receptor agonists, local ablation or oncolytic viruses is currently being evaluated in different disease settings. Despite several encouraging single arm data already presented or published, available randomized data are unimpressive. Adding PD-1/PD-L1 inhibitors to fluoropyrimidines and bevacizumab maintenance showed no beneficial impact on delaying progression. In refractory disease, the combination of PD-1/PD-L1 and MEK inhibitor was not different from regorafenib, whereas a PD-1/PD-L1 and cytotoxic T lymphocyte-associated antigen-4 inhibitor combination demonstrated better overall survival compared to supportive care alone. Clinical trials in all disease settings applying different combination approaches are ongoing and may define the role of immunotherapy in colorectal cancer.
U2 - 10.3748/wjg.v25.i29.3920
DO - 10.3748/wjg.v25.i29.3920
M3 - SCORING: Review article
C2 - 31413527
VL - 25
SP - 3920
EP - 3928
JO - WORLD J GASTROENTERO
JF - WORLD J GASTROENTERO
SN - 1007-9327
IS - 29
ER -