NeoRAS wild-type in metastatic colorectal cancer: Myth or truth?-Case series and review of the literature
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NeoRAS wild-type in metastatic colorectal cancer: Myth or truth?-Case series and review of the literature. / Osumi, Hiroki; Vecchione, Loredana; Keilholz, Ulrich; Vollbrecht, Claudia; Alig, Annabel H S; von Einem, Jobst C; Stahler, Arndt; Striefler, Jana K; Kurreck, Annika; Kind, Andreas; Modest, Dominik P; Stintzing, Sebastian; Jelas, Ivan.
In: EUR J CANCER, Vol. 153, 08.2021, p. 86-95.Research output: SCORING: Contribution to journal › SCORING: Review article › Research
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T1 - NeoRAS wild-type in metastatic colorectal cancer: Myth or truth?-Case series and review of the literature
AU - Osumi, Hiroki
AU - Vecchione, Loredana
AU - Keilholz, Ulrich
AU - Vollbrecht, Claudia
AU - Alig, Annabel H S
AU - von Einem, Jobst C
AU - Stahler, Arndt
AU - Striefler, Jana K
AU - Kurreck, Annika
AU - Kind, Andreas
AU - Modest, Dominik P
AU - Stintzing, Sebastian
AU - Jelas, Ivan
N1 - Copyright © 2021 Elsevier Ltd. All rights reserved.
PY - 2021/8
Y1 - 2021/8
N2 - Upfront KRAS and NRAS gene testing ('RAS') is the standard of care for metastatic colorectal cancer (mCRC), to guide first-line treatment. The presence of RAS mutation (MT) is a negative predictor for the efficacy of anti-EGFR antibodies and the use of cetuximab and panitumumab is restricted to RAS wild-type (WT) mCRC. Conversion from RAS WT to RAS MT mCRC after treatment with anti-EGFR antibodies is a known and well-described acquired resistance mechanism. The by far less frequent 'NeoRAS wild-type' phenomenon (reversion from RAS MT to RAS WT) has recently drawn attention. The proposed effect of chemotherapy on RAS status in mCRC patients is not fully understood. Because of the intriguing biological consequence of a RAS MT to RAS WT reversion, subsequent treatment of NeoRAS WT patients with anti-EGFR antibodies is increasingly being discussed. Here, we report three clinical cases of NeoRAS WT mCRC patients, which received standard-of-care regimens for RAS MT mCRC. Anti-EGFR antibodies were used in two out of three patients after progression of the disease. One of the patients had a long-term response. In line with our observations, NeoRAS WT phenomenon occurs in clinical practice. Retesting of RAS status during treatment should be discussed in patients with unusual long-term clinical courses of RAS MT mCRC to optimise treatment strategy and to evaluate the use of anti-EGFR antibodies.
AB - Upfront KRAS and NRAS gene testing ('RAS') is the standard of care for metastatic colorectal cancer (mCRC), to guide first-line treatment. The presence of RAS mutation (MT) is a negative predictor for the efficacy of anti-EGFR antibodies and the use of cetuximab and panitumumab is restricted to RAS wild-type (WT) mCRC. Conversion from RAS WT to RAS MT mCRC after treatment with anti-EGFR antibodies is a known and well-described acquired resistance mechanism. The by far less frequent 'NeoRAS wild-type' phenomenon (reversion from RAS MT to RAS WT) has recently drawn attention. The proposed effect of chemotherapy on RAS status in mCRC patients is not fully understood. Because of the intriguing biological consequence of a RAS MT to RAS WT reversion, subsequent treatment of NeoRAS WT patients with anti-EGFR antibodies is increasingly being discussed. Here, we report three clinical cases of NeoRAS WT mCRC patients, which received standard-of-care regimens for RAS MT mCRC. Anti-EGFR antibodies were used in two out of three patients after progression of the disease. One of the patients had a long-term response. In line with our observations, NeoRAS WT phenomenon occurs in clinical practice. Retesting of RAS status during treatment should be discussed in patients with unusual long-term clinical courses of RAS MT mCRC to optimise treatment strategy and to evaluate the use of anti-EGFR antibodies.
KW - Circulating Tumor DNA/metabolism
KW - Colorectal Neoplasms/genetics
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Neoplasm Metastasis
KW - ras Proteins/genetics
U2 - 10.1016/j.ejca.2021.05.010
DO - 10.1016/j.ejca.2021.05.010
M3 - SCORING: Review article
C2 - 34153718
VL - 153
SP - 86
EP - 95
JO - EUR J CANCER
JF - EUR J CANCER
SN - 0959-8049
ER -